Condensed heterocylic compounds and herbicides containing them

ABSTRACT

Condensed heterocyclic compounds of general formula (I) wherein T is carbon or nitrogen; when T is carbon, then the bond between T and A is a double bond, the bond between A and Y is a single bond, and Y is oxygen, sulfur, or optionally substituted NH; or when T is nitrogen, then the bond between T and A is a single bond, the bond between A and Y is a double bond, and Y is nitrogen or optionally substituted CH; A is nitrogen or optionally substituted CH; R 1  is hydrogen, halogen, alkyl, haloalkyl, hydroxymethyl, nitro, or cyano; R 2  is hydrogen, halogen, alkyl, haloalkyl, hydroxymethyl, nitro, cyano, or the like; R 3  is hydrogen, halogen, alkyl, haloalkyl, hydroxymethyl, nitro, cyano, or the like; R 4  is hydrogen, halogen, alkyl, halo-alkyl, hydroxymethyl, nitro, or cyano; and Q is a saturated or unsaturated 5- or 6- membered heterocyclic ring containing one to four nitrogen atoms, or a saturated or unsaturated cyclopentylideneamino group containing one or two nitrogen heteroatoms and one oxygen or sulfur heteroatom.

This application is the national phase under 35 U.S.C. § 371 of PCT International Application No. PCT/JP99/04758, which has an International filing date of Sep. 2, 1999, which designated the, United States of America.

TECHNICAL FIELD

The present invention relates to condensed heterocyclic compounds and their use.

DISCLOSURE OF THE INVENTION

The present inventors have extensively studied to find compounds having excellent herbicidal activity. As a result, they have found that the condensed heterocyclic compounds of general formula I as depicted below have excellent herbicidal activity, thereby completing the present invention.

The present invention provides condensed heterocyclic compounds of general formula I:

(hereinafter referred to as the present compounds)

wherein T is carbon or nitrogen; when T is carbon, then the bond between T and A is a double bond, the bond between A and Y is a single bond, and Y is oxygen, sulfur, or N—R¹⁴²; or when T is nitrogen, then the bond between T and A is a single bond, the bond between A and Y is a double bond, and Y is nitrogen or C—R¹⁵²;

wherein R¹⁴² is hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, cyano, —COR¹⁴³, —N(R¹⁴⁵)R¹⁴⁶, or —N═C(R¹⁴⁷)R¹⁴⁸; R¹⁵² is hydrogen, halogen, C₁-C₃ alkyl, nitro, amino, cyano, or —COR¹⁵³;

 wherein R¹⁴³ is hydrogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, hydroxyl, C₁-C₅ alkoxy, or —N(R¹⁵⁶)N¹⁵⁷; R¹⁴⁵ and R¹⁴⁶ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, formyl, (C₁-C₅ alkyl)carbonyl, (C₁-C₅ haloalkyl)carbonyl, or (C₁-C₆ alkoxy)carbonyl; R¹⁴⁷ and R¹⁴⁸ are independently hydrogen or C₁-C₅ alkyl; R¹⁵³ is hydrogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, hydroxyl, C₁-C₅ alkoxy, or —N(R¹⁵⁴)R¹⁵⁵;

wherein R¹⁵⁶ and R¹⁵⁷ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, formyl, (C₁-C₅ alkyl)carbonyl, (C₁-C₅ haloalkyl)carbonyl, or (C₁-C₅ alkoxy)carbonyl; R¹⁵⁴ and R¹⁵⁵ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, (C₁-C₅ alkoxy)carbonyl, formyl, (C₁-C₅ alkyl)carbonyl, or (C₁-C₅ haloalkyl)carbonyl;

A is nitrogen or C—R¹⁴¹ wherein R¹⁴¹ is hydrogen, halogen, or C₁-C₃ alkyl;

R¹ is hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, hydroxymethyl, nitro, or cyano;

R² is hydrogen, halogen, C₁-C₁₁ alkyl, C₁-C₁₁ haloalkyl, hydroxymethyl, nitro, cyano, —N(R⁹)R¹⁰, —OR¹¹, —SR¹², —SO₂R¹³, —COX, —COOR¹⁴, —CON(R¹⁵)R¹⁶, —COR¹⁷, —C(R²⁶)═NOR¹⁹, —C(R²⁷)═C(R²¹)R²², or —CH(R²³)—CH(R²⁴)R²⁵;

R³ is hydrogen, halogen, C₁-C₁₁ alkyl, C₁-C₁₁ haloalkyl, hydroxymethyl, nitro, cyano, —N(R⁵⁹)R⁶⁰, —OR⁶¹, —SR⁶², —SO₂R⁶³, —COX, —COOR⁶⁴, —CON(R⁶⁵)R⁶⁶, —COR⁶⁷, —C(R⁷⁶)═NOR⁶⁹, —C(R⁷⁷)═C(R⁷¹)R⁷², or —CH(R⁷³)—CH(R⁷⁴)R⁷⁵;

R⁴ is hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, hydroxymethyl, nitro, or cyano;

 wherein X is chlorine or bromine;

R⁹ and R⁵⁹ are independently hydrogen, C₁-C₅ alkyl, (C₁-C₅ alkyl)carbonyl, or (C₁-C₅ alkoxy)carbonyl;

R¹⁰, R¹¹, and R¹² are independently hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, cyano C₁-C₆ alkyl, (C₁-C₅ alkyl)carbonyl, (C₁-C₅ haloalkyl)carbonyl, (C₃-C₁₀ cycloalkyl)carbonyl, (C₁-C₅ alkyl)carbonyl, C₁-C₅ alkyl, (C₁-C₅ haloalkyl)carbonyl C₁-C₅ alkyl, hydroxy C₁-C₅ alkyl, C₁-C₅ alkoxy C₁-C₅ alkyl, C₁-C₅ alkylthio C₁-C₅ alkyl, (C₁-C₅ alkoxy)carbonyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, —C(R⁴³)(R⁴⁴)—C(═O)ON(R⁴⁵)R⁴⁶, —C(R⁴⁷)(R⁴⁸) —CON(R⁴⁹)R⁵⁰, —CH₂—C(R⁵⁶)═NOR⁵⁵, —CHMe—C(R⁵⁸)═NOR⁵⁷, (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkenoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, carboxy(C₁-C₅ alkyl)carbonyl, (C₁-C₁₀ alkoxy)carbonyl(C₁-C₅ alkyl)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl(C₁-C₅ alkyl)carbonyl, C₁-C₅ alkylsulfonyl, C₁-C₅ haloalkylsulfonyl, —SO₂N(R⁵¹)R⁵², —CON(R⁵³)R⁵⁴, optionally substituted benzyl, or optionally substituted phenyl;

R⁶⁰, R⁶¹, and R⁶² are independently hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, cyano C₁-C₆ alkyl, (C₁-C₅ alkyl)carbonyl, (C₁-C₅ haloalkyl)carbonyl, (C₃-C₁₀ cycloalkyl)carbonyl, (C₁-C₅ alkyl)carbonyl C₁-C₅ alkyl, (C₁-C₅ haloalkyl)carbonyl C₁-C₅ alkyl, hydroxy C₁-C₅ alkyl, C₁-C₅ alkoxy C₁-C₅ alkyl, C₁-C₅ alkylthio C₁-C₅ alkyl, (C₁-C₅ alkoxy)carbonyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₁₀ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, —C(R¹⁶³)(R¹⁶⁴)—C(═O)ON(R¹⁶⁵)R¹⁶⁶, —C(R¹⁶⁷)R¹⁶⁸)—CON(R¹⁶⁹)R¹⁷⁰, —CH₂—C(═NOR¹⁷⁵)R¹⁷⁶, —CHMe—C(═NOR¹⁷⁷)R¹⁷⁸, (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkenoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, carboxy(C₁-C₅ alkyl)carbonyl, (C₁-C₁₁₀ alkoxy)carbonyl(C₁-C₅ alkyl)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl(C₁-C₅ alkyl)carbonyl, C₁-C₅ alkylsulfonyl, C₁-C₅ haloalkylsulfonyl, —SO₂N(R¹⁷¹)R¹⁷², —CON(R¹⁷³)R¹⁷⁴, optionally substituted benzyl, or optionally substituted phenyl;

 wherein R⁴³, R⁴⁴, R¹⁶³, and R¹⁶⁴ are independently hydrogen, halogen, C₁-C₅ alkyl, or C₁-C₅ haloalkyl;

R⁴⁵, R⁴⁶, R¹⁶⁵, and R¹⁶⁶ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁴⁵ and R⁴⁶ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring, or R¹⁶⁵ and R¹⁶⁶ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring;

R⁴⁷, R⁴⁸, R¹⁶⁷, and R¹⁶⁸ are independently hydrogen, halogen, C₁-C₅ alkyl, or C₁-C₅ haloalkyl;

R⁴⁹, R⁵⁰, R¹⁶⁹, and R¹⁷⁰ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁴⁹ and R⁵⁰ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R¹⁶⁹ and R¹⁷⁰ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R⁵¹, R⁵², R¹⁷¹, and R¹⁷² are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁵¹ and R⁵² may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R¹⁷¹ and R¹⁷² may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R⁵³, R⁵⁴, R¹⁷³, and R¹⁷⁴ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁵³ and R⁵⁴ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R¹⁷³ and R¹⁷⁴ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated, ring containing zero to one oxygen atom or NH group in the ring;

R⁵⁵, R⁵⁷, R¹⁷⁵, and R¹⁷⁷ are independently hydrogen or C₁-C₃ alkyl;

R⁵⁶, R⁵⁸, R¹⁷⁶, and R¹⁷⁸ are independently hydrogen, C₁-C₅ alkyl, (C₁-C₅ alkoxy)carbonyl, (C₁-C₅ haloalkoxy)carbonyl, (C₃-C₅ cycloalkoxy)carbonyl, (C₃-C₅ alkenoxy)carbonyl, or (C₃-C₅ alkynoxy)carbonyl;

R¹³ is hydroxy, chlorine, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, —N(R⁷⁹)R⁸⁰, or —OR⁸¹;

R⁶³ hydroxy, chlorine, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, —N(R¹⁷⁹)R¹⁸⁰, or —OR¹⁸¹;

 wherein R⁷⁹ and R¹⁷⁹ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R⁸⁰ and R¹⁸⁰ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁷⁹ and R⁸⁰ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R¹⁷⁹ and R¹⁸⁰ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; and R⁸¹ and R¹⁸¹ are independently C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl;

R¹⁴ is hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl, —N(R⁸²)R⁸³, optionally substituted benzyl, or optionally substituted phenyl;

R⁶⁴ is hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl, —N(R¹⁸²)R¹⁸³, optionally substituted benzyl, or optionally substituted phenyl;

 wherein R⁸² and R¹⁸² are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R⁸³ and R¹⁸³ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁸² and R⁸³ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R¹⁸² and R¹⁸³ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R¹⁵ and R⁶⁵ are independently hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ alkynyl, cyano C₁-C₆ alkyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, optionally substituted benzyl, or optionally substituted phenyl; R¹⁶ and R⁶⁶ are independently hydrogen, C₁-C₁₀ alkyl, or C₁-C₁₀ haloalkyl; or R¹⁵ and R¹⁶ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R⁶⁵ and R⁶⁶ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R¹⁷, R²⁶, R²⁷, R⁶⁷, R⁷⁶, and R⁷⁷ are independently hydrogen, cyano, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, (C₁-C₆ alkoxy)carbonyl, or (C₁-C₆ alkoxy)carbonylmethyl;

R¹⁹ and R⁶⁹ are independently hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, cyano C₁-C₆ alkyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl;

R²¹ and R⁷¹ are independently hydrogen, halogen, C₁-C₃ alkyl, or C₁-C₃ haloalkyl;

R²² and R²⁵ are independently carboxy, (C₁-C₁₀ alkoxy)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl, (C₃-C₁₀ cycloalkoxy)carbonyl, (C₃-C₁₀ halocycloalkoxy)carbonyl, carboxy(C₁-C₅ alkoxy)carbonyl, (C₁-C₁₀ alkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ cycloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ alkenoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ alkynoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, —CON(R⁸⁴)R⁸⁵, or —C(═O)ON(R⁸⁶)R⁸⁷;

R⁷² and R⁷⁵ are independently carboxy, (C₁-C₁₀ alkoxy)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl, (C₃-C₁₀ cycloalkoxy)carbonyl, (C₃-C₁₀ halocycloalkoxy)carbonyl, carboxy(C₁-C₅ alkoxy)carbonyl, (C₁-C₁₀ alkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ cycloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ alkenoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ alkynoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, —CON(R¹⁸⁴R¹⁸⁵, or —C(═O)ON(R¹⁸⁶)R¹⁸⁷;

 wherein R⁸⁴ and R¹⁸⁴ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R⁸⁵ and R¹⁸⁵ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁸⁴ and R⁸⁵ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R¹⁸⁴ and R¹⁸⁵ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring;

R⁸⁶ and R¹⁸⁶ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R⁸⁷ and R¹⁸⁷ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁸⁶ and R⁸⁷ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; or R¹⁸⁶ and R¹⁸⁷ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring;

R²³, R²⁴, R⁷³, and R⁷⁴ are independently hydrogen, halogen, C₁-C₃ alkyl, or C₁-C₃ haloalkyl; and

Q is any one group of Q1 to Q23 of the general formula:

 wherein:

in Q1, E¹ and E² are independently C₁-C₆ alkyl optionally substituted with halogen, or C₃-C₆ cycloalkyl optionally substituted with halogen; or E¹ and E² may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen;

in Q2, E³ and E⁴ are independently C₁-C₆ alkyl optionally substituted with halogen, or C₃-C₆ cycloalkyl optionally substituted with halogen; or E³ and E⁴ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; D¹ and D² are independently oxygen or sulfur; and Z¹ is nitrogen or CH;

in Q3, E⁵ is hydrogen or C₁-C₆ alkyl optionally substituted with halogen; and D³ is oxygen or sulfur;

in Q4, E⁶ and E⁷ are independently hydrogen, C₁-C₆ alkyl optionally substituted with halogen, or C₃-C₆ cycloalkyl optionally substituted with halogen; or E⁶ and E⁷ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen;

in Q5, E⁸ and E⁹ are independently hydrogen, C₁-C₆ alkyl optionally substituted with halogen, or C₃-C₆ cycloalkyl optionally substituted with halogen; or E⁸ and E⁹ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen;

in Q6, E¹⁰ is hydrogen, C₁-C₆ alkyl optionally substituted with halogen, or C₁-C₃ alkoxy optionally substituted with halogen; E¹¹ is hydrogen or C₁-C₆ alkyl optionally substituted with halogen; or E¹⁰ and E¹¹ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen; and E⁴⁴ is halogen or C₁-C₃ alkyl;

in Q7, E¹² is C₁-C₆ alkyl optionally substituted with halogen; and D⁴ is oxygen or sulfur;

in Q8, E¹³ is C₁-C₆ alkyl optionally substituted with halogen; and E¹⁴ is hydrogen or halogen;

in Q9, E¹⁵ is hydrogen or C₁-C₆ alkyl; E¹⁶ is C₁-C₆ alkyl optionally substituted with halogen; or E¹⁵ and E¹⁶ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen;

in Q10, E¹⁷, E¹⁸, and E¹⁹ are independently hydrogen or C₁-C₆ alkyl; and D⁵ is oxygen or sulfur;

in Q11, E²⁰ and E²¹ are independently hydrogen or C₁-C₆ alkyl; and D⁶ is oxygen or sulfur;

in Q12, E²² and E²³ are independently hydrogen or C₁-C₆ alkyl;

in Q13, E²⁴ is hydrogen or C₁-C₃ alkyl;

in Q14, E²⁵ is hydrogen, C₁-C₃ alkyl, or halogen; E²⁶ is C₁-C₃ alkyl optionally substituted with halogen; E²⁷ is hydrogen, amino, C₁-₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, or optionally substituted benzyl; and D⁷ is oxygen or sulfur;

in Q15, E²⁸ is C₁-C₃ alkyl optionally substituted with halogen; E²⁹ is hydrogen, amino, C₁-C₆ alkyl, C₁-C₆ alkenyl, C₃-C₆ alkynyl, or optionally substituted benzyl; and D⁸ is oxygen or sulfur;

in Q16, E³⁰ is C₁-C₃ alkyl optionally substituted with halogen, E³¹ is hydrogen or C₁-C₃ alkyl optionally substituted with halogen; or E³⁰ and E³¹ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring (which unsaturated ring includes no aromatic rings), and the ring may optionally be substituted with methyl or halogen; and E⁴² is hydrogen or C₁-C₃ alkyl optionally substituted with halogen;

in Q17, E³² is C₁-C₃ alkyl optionally substituted with halogen; E³³ is hydrogen, halogen, amino, C₁-C₃ alkyl optionally substituted with halogen, C₁-C₃ alkoxy optionally substituted with halogen, or C₁-C₃ alkylthio optionally substituted with halogen; and E⁴³ is hydrogen or C₁-C₃ alkyl optionally substituted with halogen;

in Q18, E³⁴ is C₁-C₃ alkyl optionally substituted with halogen;

in Q19, D⁹ is oxygen or sulfur; and V¹ is —CH₂—, —CH₂—CH₂—, or —CH₂—CH₂—CH₂—;

in Q20, E³⁵ is C₁-C₃ alkyl optionally substituted with halogen; Z² is nitrogen or CH; and V² is —CH₂—CH₂—, —CH═CH—, —N═CH—, —CH═N—, or —N═N—;

in Q21, E³⁶ and E³⁷ are independently C₁-C₆ alkyl; or E³⁶ and E³⁷ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; D¹⁰ and D¹¹ are independently oxygen or sulfur; and Z³ is nitrogen or CH;

in Q22, E³⁸ is hydrogen or C₁-C₆ alkyl; E³⁹ is C₁-C₃ alkyl optionally substituted with halogen; or E³⁸ and E³⁹ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; and D¹² is oxygen or sulfur; and

in Q23, E⁴⁰ is hydrogen or C₁-C₆ alkyl; E⁴¹ is C₁-C₃ alkyl, or C₃-C₆ cycloalkyl; or E⁴⁰ and E⁴¹ may be combined at their ends to form, together with the atoms attached thereto, a 4- to 7-membered saturated or unsaturated ring containing zero to two O, S, SO, SO₂, or NH groups in the ring, and the ring may optionally be substituted with methyl or halogen; and D¹³ is oxygen or sulfur.

The present invention further provides herbicides containing them as active ingredients, and condensed heterocyclic compounds of general formula II:

wherein A¹ is C—R³¹ and Y¹¹ is oxygen, sulfur, or N—R³²; wherein R³¹ is nitro, amino, cyano, carboxyl, or (C₁-C₃ alkoxy)carbonyl, and R³² is hydrogen, C₁-C₅ alkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; and Q, R¹, R², R³, and R⁴ are as defined above, which heterocyclic compounds are useful as intermediates for the production of the present compounds.

Mode for Carrying Out the Invention

For the groups represented by R¹⁴², C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

For the groups-represented by R¹⁴³, C₁-C₃ alkyl may include methyl, ethyl, propyl, and isopropyl; C₁-C₃ haloalkyl may include trifluoromethyl and difluoromethyl; and C₁-C₅ alkoxy may include methoxy, ethoxy, propoxy, and isopropoxy.

For the groups represented by R¹⁴⁵ or R¹⁴⁶, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C₁-C₅ alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C₁-C₅ haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C₁-C₅ alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.

For the groups represented by R¹⁴⁷ or R¹⁴⁸, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.

For the elements or groups represented by R¹⁵², halogen may include fluorine, chlorine, bromine, and iodine; and C₁-C₃ alkyl may include methyl, ethyl, propyl, and isopropyl.

For the groups represented by R¹⁵³, C₁-C₃ alkyl may include methyl, ethyl, propyl, and isopropyl; C₁-C₃ haloalkyl may include trifluoromethyl and difluoromethyl; and C₁-C₅ alkoxy may include methoxy, ethoxy, propoxy, and isopropoxy.

For the groups represented by R¹⁵⁶ or R¹⁵⁷, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C₁-C₅ alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C₁-C₅ haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C₁-C₅ alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.

For the groups represented by R¹⁵⁴ or R¹⁵⁵, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; (C₁-C₅ alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C₁-C₅ haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; and (C₁-C₅ alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and isopropoxycarbonyl.

For the groups or elements represented by R¹⁴¹, C₁-C₃ alkyl may include methyl, ethyl, and isopropyl; and halogen may include fluorine, chlorine, bromine, and iodine.

For groups represented by R³¹, (C₁-C₃ alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, and isopropoxycarbonyl.

For the groups represented by R³², C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

For the elements or groups represented by R¹, halogen may include fluorine, chlorine, bromine, and iodine; C₁-C₃ alkyl may include methyl and ethyl; and C₁-C₃ haloalkyl may include trifluoromethyl and difluoromethyl.

For the elements or groups represented by R² or R³, halogen may include fluorine, chlorine, bromine, and iodine; C₁-C₁₁ alkyl may include methyl, ethyl, and isopropyl; and C₁-C₁₁ haloalkyl may include trichloromethyl, trifluoromethyl, chlorodifluoromethyl, difluoromethyl, pentafluoroethyl, and 1,1-difluoroethyl.

For the elements or groups represented by R⁴, halogen may include fluorine, chlorine, bromine, and iodine; C₁-C₃ alkyl may include methyl and ethyl; and C₁-C₃ haloalkyl may include trifluoromethyl and difluoromethyl.

For the groups represented by R⁹ or R⁵⁹, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl (wherein “t” means “tertiary”; this also holds below), and isoamyl; (C₁-C₅ alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; and (C₁-C₅ alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, and t-butoxycarbonyl.

For the groups represented by R¹⁰, R¹¹, R¹², R⁶⁰, R⁶¹, or R⁶², C₁-C₁₀ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C₁-C₁₀ haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C₃-C₁₀ cycloalkyl may include cyclopentyl and cyclohexyl; C₁-C₁₀ halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C₃-C₁₀ cycloalkyl C₁-C₃ alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C₃-C₁₀ alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C₃-C₁₀ haloalkenyl may include 2-chloro-2-propenyl and 3,3-dichloro-2-propenyl; C₃-C₁₀ alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C₃-C₁₀ haloalkynyl may include 3-iodo-2-propynyl and 3-bromo-2-propynyl; cyano C₁-C₆ alkyl may include cyanomethyl and cyanoethyl; (C₁-C₅ alkyl)carbonyl may include acetyl, ethylcarbonyl, propylcarbonyl, isopropylcarbonyl, and butylcarbonyl; (C₁-C₅ haloalkyl)carbonyl may include trifluoroacetyl, difluoroacetyl, chlorodifluoroacetyl, and dichloroacetyl; (C₃-C₁₀ cycloalkyl)carbonyl may include cyclopropylcarbonyl and cyclopentylcarbonyl; (C₁-C₅ alkyl)carbonyl C₁-C₅ alkyl may include 2-oxopropyl, 3-methyl-2-oxobutyl, and 3-oxopentyl; (C₁-C₅ haloalkyl)carbonyl C₁-C₅ alkyl may include 3,3,3-trifluoro-2-oxopropyl; hydroxy C₁-C₅ alkyl may include 2-hydroxyethyl and 4-hydroxybutyl; C₁-C₅ alkoxy C₁-C₅ alkyl may include methoxymethyl, 1-methoxyethyl, and ethoxymethyl; C₁-C₅ alkylthio C₁-C₅ alkyl may include methylthiomethyl and methylthioethyl; (C₁-C₅ alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, and t-butoxycarbonyl; carboxy C₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonyl; (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl may include 4-fluorocyclohexyloxycarbonylmethyl; (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl may include allyoxycarbonylmethyl, 1-methyl-2-propenyloxycarbonylmethyl, 1-allyloxycarbonylethyl, and 1-(1-methyl-2-propenyloxy)carbonylethyl; (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl may include propargyloxycarbonylmethyl, 1-methyl-2-propynyloxycarbonylmethyl, 1-propargyloxycarbonylethyl, 1-(1-methyl-2-propynyloxy)carbonylethyl; carboxy(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl may include carboxymethoxycarbonylmethyl, 1-carboxyethoxycarbonylmethyl, 1-carboxy-1-methylethoxycarbonylmethyl, 1-(carboxymethoxycarbonyl)ethyl, 1-(1-carboxyethoxycarbonyl)ethyl, and 1-(1-carboxy-1-methylethoxy-carbonyl)ethyl; (C₁-C₁₀ alkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethoxycarbonylmethyl, 1-methoxycarbonylethoxycarbonylmethyl, 1-methoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(methoxycarbonylmethoxycarbonyl)ethyl, 1-(1-methoxycarbonylethoxycarbonyl)ethyl, 1-(1-methoxycarbonyl-1-methylethoxycarbonyl)ethyl, ethoxycarbonylmethoxycarbonylmethyl, 1-ethoxycarbonylethoxycarbonylmethyl, 1-ethoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(ethoxycarbonylmethoxycarbonyl)ethyl, 1-(1-ethoxycarbonylethoxycarbonyl)ethyl, 1-(1-ethoxycarbonyl-1-methylethoxycarbonyl)ethyl, isopropoxycarbonylmethoxy-carbonylmethyl, 1-isopropoxycarbonylethoxycarbonylmethyl, 1-isopropoxycarbonyl-1-methylethoxycarbonylmethyl, 1-(isopropoxycarbonylmethoxycarbonyl)ethyl, 1-(1-isopropoxycarbonylethoxycarbonyl)ethyl, and 1-(1-isopropoxycarbonyl-1-methylethoxycarbonyl)ethyl; (C₁-C₁₀ haloalkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethoxycarbonylmethyl, 1-(2-chloroethoxycarbonyl)ethoxycarbonylmethyl, 1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonylmethyl, 1-(2-chloroethoxycarbonylmethoxycarbonyl)ethyl, 1-{1-(2-chloroethoxycarbonyl)ethoxycarbonyl}ethyl, and 1-{1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonyl}-ethyl; (C₃-C₁₀ cycloalkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethoxycarbonylmethyl, 1-cyclopentyloxycarbonylethoxycarbonylmethyl, 1-cyclopentyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(cyclopentyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-cyclopentyloxycarbonylethoxycarbonyl)ethyl, 1-(1-cyclopentyloxycarbonyl-1-methylethoxycarbonyl)ethyl, cyclohexyloxycarbonylmethoxycarbonylmethyl, 1-cyclohexyloxycarbonylethoxycarbonylmethyl, 1-cyclohexyloxycarbonyl-1-ethylethoxycarbonylmethyl, 1-(cyclohexyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-cyclohexyloxycarbonylethoxycarbonyl)ethyl, and 1-(1-cyclohexyloxycarbonyl-1-methylethoxycarbonyl)ethyl; (C₃-C₁₀ alkenoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl may include allyloxycarbonylmethoxycarbonylmethyl, 1-allyloxycarbonylethoxycarbonylmethyl, 1-allyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(allyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-allyloxycarbonylethoxycarbonyl)ethyl, and 1-(1-allyloxycarbonyl-1-methylethoxycarbonyl)ethyl; (C₃-C₁₀ alkynoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl may include propargyloxycarbonylmethoxycarbonylmethyl, 1-propargyloxycarbonylethoxycarbonylmethyl, 1-propargyloxycarbonyl-1-methylethoxycarbonylmethyl, 1-(propargyloxycarbonylmethoxycarbonyl)ethyl, 1-(1-propargyloxycarbonylethoxycarbonyl)ethyl, and 1-(1-propargyloxycarbonyl-1-methylethoxycarbonyl)ethyl; carboxy(C₁-C₅ alkyl)carbonyl may include carboxymethylcarbonyl, carboxyethylcarbonyl, 1-carboxy-1-methylethylcarbonyl, 2-carboxyethylcarbonyl, 3-carboxypropylcarbonyl, and 3-carboxy-1-methylpropylcarbonyl; (C₁-C₁₀ alkoxy)carbonyl(C₁-C₅ alkyl)carbonyl may include methoxycarbonylmethylcarbonyl, 1-methoxycarbonylethylcarbonyl, 1-methoxycarbonyl-1-methylethylcarbonyl, 2-methoxycarbonylethylcarbonyl, 3-methoxycarbonylpropylcarbonyl, 3-methoxycarbonyl-1-methylpropylcarbonyl, ethoxycarbonylmethylcarbonyl, 1-ethoxycarbonylethylcarbonyl, 1-ethoxycarbonyl-1-methylethylcarbonyl, 2-ethoxycarbonylethylcarbonyl, 3-ethoxycarbonylpropylcarbonyl, and 3-ethoxycarbonyl-1-methylpropylcarbonyl; (C₁-C₁₀ haloalkoxy)carbonyl(C₁-C₅ alkyl)carbonyl may include 2-chloroethoxycarbonylmethylcarbonyl, 2,2,2-trifluoroethoxycarbonylmethylcarbonyl, 3-bromopropoxycarbonylmethylcarbonyl, 1-(2-chloroethoxy)carbonylethylcarbonyl, and 1-(2,2,2-trifluoroethoxy)carbonylethylcarbonyl; C₁-C₅ alkylsulfonyl may include methylsulfonyl, ethylsulfonyl, propylsulfonyl, isopropylsulfonyl, and butylsulfonyl; C₁-C₅ haloalkylsulfonyl may include chloromethylsulfonyl, and trifluoromethylsulfonyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.

For the groups represented by R¹³ or R⁶³, C₁-C₁₀ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, and isoamyl; C₁-C₁₀ haloalkyl may include trifluoromethyl; carboxy C₁-C₅ alkyl may include carboxymethyl, carboxyethyl, 1-carboxyethyl, and 2-carboxypropyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxyvcarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl may include 4-fluorocyclo hexyloxycarbonylmethyl.

For the groups represented by R¹⁴ or R⁶⁴, C₁-C₁₀ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C₁-C₁₀ haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C₃-C₁₀ cycloalkyl may include cyclopentyl and cyclohexyl; C₃-C₁₀ halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C₃-C₁₀ cycloalkyl C₁-C₃ alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C₃-C₁₀ alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C₃-C₁₀ haloalkenyl may include 2-chloro-2-propenyl, and 3,3-dichloro-2-propenyl; C₃-C₁₀ alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C₃-C₁₀ haloalkynyl may include 3-iodo-2-propynyl, and 3-bromo-2-propynyl; carboxy C₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, 2-carboxyethyl, and 1-carboxy-1-methylethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonyl methyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-methoxycarbonyl-1-methylethyl, 1-ethoxycarbonyl-1-methylethyl, 1-propoxycarbonyl-1-methylethyl, 1-isopropoxycarbonyl-1-methylethyl, 1-butoxycarbonyl-1-methylethyl, 1-isobutoxycarbonyl-1-methylethyl, 1-t-butoxycarbonyl-1-methylethyl, 1-amyloxycarbonyl-1-methylethyl, 1-isoamyloxycarbonyl-1-methylethyl, and 1-t-butoxycarbonyl-1-methylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, 1-(2,2,2-trifluoroethoxy)carbonylethyl, 1-(2-chloroethoxy)carbonyl-1-methylethyl, and 1-(2,2,2-trifluoroethoxy)carbonyl-1-methylethyl; (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, 1-cyclohexyloxycarbonylethyl, 1-cyclopentyloxycarbonyl-1-methylethyl, and 1-cyclohexyloxycarbonyl-1-methylethyl; (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl may include 4-fluorocyclohexyloxycarbonylmethyl, and 1-(4-fluorocyclohexyloxycarbonyl)-1-methylethyl; (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl may include allyloxycarbonylmethyl, 1-methyl-2-propenyloxycarbonylmethyl, 1-allyloxycarbonylethyl, 1-(1-methyl-2-propenyloxy)carbonylethyl, 1-allyloxycarbonyl-1-methylethyl, and 1-(1-methyl-2-propenyloxy)carbonyl-1-methylethyl; (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl may include propargyloxycarbonylmethyl, 1-methyl-2-propynyloxycarbonylmethyl, 1-propargyloxycarbonylethyl, 1-(1-methyl-2-propynyloxy)carbonylethyl, 1-propargyloxycarbonyl-1-methylethyl, and 1-(1-methyl-2-propynyloxy)carbonyl-1-methylethyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.

For the groups represented by R¹⁵ or R⁶⁵, C₁-C₁₀ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C₁-C₁₀ haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C₃-C₁₀ cycloalkyl may include cyclopentyl, and cyclohexyl; C₃-C₁₀ cycloalkyl C₁-C₃ alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C₃-C₁₀ alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C₃-C₁₀ alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; cyano C₁-C₆ alkyl may include cyanomethyl, and cyanoethyl; carboxyC₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; optionally substituted benzyl may include benzyl; and optionally substituted phenyl may include phenyl.

For the groups represented by R¹⁶ or R⁶⁶, C₁-C₁₀ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; and C₁-C₁₀ haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl.

The 3- to 7-membered saturated ring, which is formed by combining R¹⁵ and R¹⁶ or R⁶⁵ and R⁶⁶ at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

For the groups represented by R¹⁷, R²⁶, R²⁷, R⁶⁷, R⁷⁶, or R⁷⁷, C₁-C₁₀ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C₁-C₁₀ haloalkyl may include 2-fluoroethyl, 2-chloroethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifuoroethyl; C₃-C₁₀ cycloalkyl may include cyclopentyl, and cyclohexyl; C₃-C₁₀ cycloalkyl C₁-C₃ alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; (C₁-C₆ alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, and isopro-poxycarbonyl; and (C₁-C₆ alkoxy)carbonylmethyl may include methoxy carbonylmethyl, ethoxycarbonylmethyl, and isopropoxycarbonylmethyl.

For the groups represented by R¹⁹ or R⁶⁹, C₁-C₁₀ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, t-butyl, isoamyl, pentyl, hexyl, heptyl, and octyl; C₁-C₁₀ haloalkyl may include 2-fluoroethyl, 2-chloro-ethyl, 2-bromoethyl, 3-chlorobutyl, 3-bromobutyl, difluoromethyl, and 2,2,2-trifluoroethyl; C₃-C₁₀ cycloalkyl may include cyclopentyl and cyclohexyl; C₃-C₁₀ halocycloalkyl may include 4,4,-difluorocyclopentyl and 3-chlorocyclohexyl; C₃-C₁₀ cycloalkyl C₁-C₃ alkyl may include cyclopropylmethyl, cyclopentylmethyl, and cyclohexylmethyl; C₃-C₁₀ alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C₃-C₁₀ haloalkenyl may include 2-chloro-2-propenyl, and 3,3-dichloro-2-propenyl; C₃-C₁₀ alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; C₃-C₁₀ haloalkynyl may include 3-iodo-2-propynyl, and 3-bromo-2-propynyl; cyano C₁-C₆ alkyl may include cyanomethyl and cyanoethyl; carboxy C₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

For the elements or groups represented by R²¹ or R⁷¹, halogen may include fluorine, chlorine, bromine, and iodine; C₁-C₃ alkyl may include methyl and ethyl; and C₁-C₃ haloalkyl may include trifluoromethyl.

For the groups represented by R²², R²⁵, R⁷², or R⁷⁵, (C₁-C₁₀ alkoxy) carbonyl may include methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, butoxycarbonyl, t-butoxycarbonyl, amyloxycarbonyl, and isoamyloxycarbonyl; (C₁-C₁₀ haloalkoxy)carbonyl may include 2-chloroethoxycarbonyl, 2-fluoroethoxycarbonyl, 3-bromopropoxycarbonyl, 3-chlorobutoxycarbonyl, and 5,5-dichloroamyloxycarbonyl; (C₃-C₁₀ cycloalkoxy)carbonyl may include cyclopentyloxycarbonyl and cyclohexylcarbonyl; (C₃-C₁₀ halocycloalkoxy)carbonyl may include 4,4-difluorocyclohexyloxycarbonyl; carboxy(C₁-C₅ alkoxy)carbonyl may include carboxymethoxycarbonyl, 1-carboxyethoxycarbonyl, and 1-carboxy-1-methylethoxycarbonyl; (C₁-C₁₀ alkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl may include methoxycarbonylmethoxycarbonyl, 1-methoxycarbonylethoxycarbonyl, 1-methoxycarbonyl-1-methylethoxycarbonyl, ethoxycarbonylmethoxycarbonyl, 1-ethoxycarbonylethoxycarbonyl, 1-ethoxycarbonyl-1-methylethoxycarbonyl, isopropoxycarbonylmethoxycarbonyl, 1-isopropoxycarbonylethoxycarbonyl, and 1-isopropoxycarbonyl-1-methylethoxycarbonyl; (C₁-C₁₀ haloalkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl may include 2-chloroethoxycarbonylmethoxycarbonyl, 1-(2-chloroethoxycarbonyl)ethoxycarbonyl, and 1-(2-chloroethoxycarbonyl)-1-methylethoxycarbonyl; (C₃-C₁₀ cycloalkoxy)carbonyl(C₁-C₅ alkoxy)carbonyl may include cyclopentyloxycarbonylmethoxycarbonyl, 1-cyclopentyloxycarbonylethoxycarbonyl, 1-cyclopentyloxycarbonyl-1-methylethoxycarbonyl, cyclohexyloxycarbonylmethoxycarbonyl, 1-cyclohexyloxycarbonylethoxycarbonyl, and 1-cyclohexyloxycarbonyl-1-methylethoxycarbonyl; (C₃-C₁₀ alkenoxy)carbonyl(C₁-C₅ alkoxy)carbonyl may include allyloxycarbonylmethoxycarbonyl, 1-allyloxycarbonylethoxycarbonyl, and 1-allyloxycarbonyl-1-methylethoxycarbonyl; and (C₃-C₁₀ alkynoxy)carbonyl(C₁-C₅ alkoxy)carbonyl may include propargyloxycarbonylmethoxycarbonyl, 1-propargyloxycarbonylethoxycarbonyl, and 1-propargyloxycarbonyl-1-methylethoxycarbonyl

For the elements or groups represented by R²³, R²⁴, R⁷³, or R⁷⁴, halogen may include fluorine, chlorine, bromine, and iodine; C₁-C₃ alkyl may include methyl, and ethyl; and C₁-C₃ haloalkyl may include trifluoromethyl.

For the elements or groups represented by R⁴³, R⁴⁴, R¹⁶³, or R¹⁶⁴, halogen may include fluorine, chlorine, bromine, and iodine; C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; and C₁-C₅ haloalkyl may include trifluoromethyl.

For the groups represented by R⁴⁵, R⁴⁶, R¹⁶⁵, or R¹⁶⁶, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

The 3- to 7-membered saturated ring, which is formed by combining R⁴⁵, and R⁴⁶ or R¹⁶⁵ and R¹⁶⁶ at their ends, together with the adjacent nitrogen atom, may include aziridine ring, azetidine ring, pyrrolidine ring, and piperidine ring.

For the elements and groups represented by R⁴⁷, R⁴⁸, R¹⁶⁷, or R¹⁶⁸, halogen may include fluorine, chlorine, bromine, and iodine; C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; and C₁-C₅ haloalkyl may include trifluoromethyl.

For the groups represented by R⁴⁹, R⁵⁰, R¹⁶⁹, or R¹⁷⁰, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl, and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

The 3- to 7-membered ring, which is formed by combining R⁴⁹ and R⁵⁰ or R¹⁶⁹ and R¹⁷⁰ at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

For the groups represented by R⁵¹, R⁵², R¹⁷¹, or R¹⁷², C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

The 3- to 7-membered ring, which is formed by combining R⁵¹ and R⁵² or R¹⁷¹ and R¹⁷² at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

For the groups represented by R⁵³, R⁵⁴, R¹⁷³, or R¹⁷⁴, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

The 3- to 7-membered ring, which is formed by combining R⁵³ and R⁵⁴ or R¹⁷³ and R¹⁷⁴ at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

For the groups represented by R⁵⁵, R⁵⁷, R¹⁷⁵, or R¹⁷⁷, C₁-C₃ alkyl may include methyl, ethyl, and propyl.

For the groups represented by R⁵⁵, R⁵⁷, R¹⁷⁵, or R¹⁷⁷, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; (C₁-C₅ alkoxy)carbonyl may include methoxycarbonyl, ethoxycarbonyl, and propyloxycarbonyl; (C₁-C₅ haloalkoxy)carbonyl may include trifluoromethoxycarbonyl and 2,2,2-trifluoroethoxycarbonyl; (C₃-C₅ cycloalkoxy)carbonyl may include cyclopropyloxycarbonyl; (C₃-C₅ alkenoxy)carbonyl may include allyloxycarbonyl; and (C₃-C₅ alkynoxy)carbonyl may include propargyloxycarbonyl.

For the groups represented by R⁷⁹ or R¹⁷⁹, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl; carboxy C₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C₃-C¹⁰ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C₃-C₁₀ halocycloalkoxy) carbonyl C₁-C₅ alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

For the groups represented by R⁸⁰ or R¹⁸⁰, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

The 3- to 7-membered ring, which is formed by combining R⁷⁹ and R⁸⁰ or R¹⁷⁹ and R¹⁸⁰ at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

For the groups represented by R⁸¹ or R¹⁸¹, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl; carboxy C₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1(2,2,2-trifluoroethoxy)carbonylethyl; (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

For the groups represented by R⁸² or R¹⁸², C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl; carboxy C₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

For the groups represented by R⁸³ or R¹⁸³, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include; allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1methylpropynyl.

The 3- to 7-membered ring, which is formed by combining R⁸² and R⁸³ or R¹⁸² and R¹⁸³ at their ends, together with the adjacent nitrogen, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

For the groups represented by R⁸⁴ or R¹⁸⁴, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl; carboxy C₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl, ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

For the groups represented by R⁸⁵ or R¹⁸⁵, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

The 3- to 7-membered ring, which is formed by combining R⁸⁴ and R⁸⁵ or R¹⁸⁴ and R¹⁸⁵ at their ends, together with the adjacent nitrogen atom, and which contains zero to one oxygen atom or NH group in the ring, may include aziridine ring, azetidine ring, pyrrolidine ring, piperidine ring, morpholine ring, and piperazine ring.

For the groups represented by R⁸⁶ or R¹⁸⁶, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl; carboxy C₁-C₅ alkyl may include carboxymethyl, 1-carboxyethyl, and 2-carboxyethyl; (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl may include methoxycarbonylmethyl. ethoxycarbonylmethyl, propoxycarbonylmethyl, isopropoxycarbonylmethyl, butoxycarbonylmethyl, isobutoxycarbonylmethyl, t-butoxycarbonylmethyl, amyloxycarbonylmethyl, isoamyloxycarbonylmethyl, t-amyloxycarbonylmethyl, 1-methoxycarbonylethyl, 1-ethoxycarbonylethyl, 1-propoxycarbonylethyl, 1-isopropoxycarbonylethyl, 1-butoxycarbonylethyl, 1-isobutoxycarbonylethyl, 1-t-butoxycarbonylethyl, 1-amyloxycarbonylethyl, 1-isoamyloxycarbonylethyl, and 1-t-butoxycarbonylethyl; (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl may include 2-chloroethoxycarbonylmethyl, 2,2,2-trifluoroethoxycarbonylmethyl, 3-bromopropoxycarbonylmethyl, 1-(2-chloroethoxy)carbonylethyl, and 1-(2,2,2-trifluoroethoxy)carbonylethyl; (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl may include cyclopentyloxycarbonylmethyl, cyclohexyloxycarbonylmethyl, 1-cyclopentyloxycarbonylethyl, and 1-cyclohexyloxycarbonylethyl; and (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl may include 4-fluorocyclohexyloxycarbonylmethyl.

For the groups represented by R⁸⁷ or R¹⁸⁷, C₁-C₅ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl; C₁-C₅ haloalkyl may include 2-chloroethyl, 2-fluoroethyl, 2,2,2-trifluoroethyl, 2,2,2-trichloroethyl, and 3-bromopropyl; C₃-C₈ cycloalkyl may include cyclopentyl, cyclohexyl, and cycloheptyl; C₃-C₆ alkenyl may include allyl and 1-methylpropenyl; and C₃-C₆ alkynyl may include propargyl and 1-methylpropynyl.

The 3- to 7-membered ring, which is formed by combining R⁸⁶ and R⁸⁷ or R¹⁸⁶ and R¹⁸⁷ at their ends, together with the adjacent nitrogen atom, may include aziridine ring, azetidine ring, pyrrolidine ring, and piperidine ring.

For the groups represented by E¹ or E², C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, and chlorodifluoromethyl; and C₃-C₆ cycloalkyl optionally substituted with halogen may include cyclopropyl cyclobutyl, and cyclopentyl.

The 4- to 7-membered unsaturated rig, which is formed by combining E¹ and E² at their ends and which contains, together with the atoms attached thereto on Q1, zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E¹ and E²

For the groups represented by E³ or E⁴, C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C₃-C₆ cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.

The 4- or 7-membered saturated or unsaturated ring, which is formed by combining E³ and E⁴ at their ends and which contains, together with the atoms attached thereto on Q2, zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E³ and E⁴.

For the groups represented by E⁵, C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, 2-fluoroethyl, 3-fluoropropyl, and 4-fluorobutyl.

For the groups or elements represented by E⁶ or E⁷, C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C₃-C₆ cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.

The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E⁶ and E⁷ at their ends and which contains, together with the atoms attached thereto on Q4, zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E⁶ and E⁷.

For the groups represented by E⁸ or E⁹, C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C₃-C₆ cycloalkyl optionally substituted with halogen may include cyclopropyl, cyclobutyl, and cyclopentyl.

The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E⁸ and E⁹ at their ends and which contains, together with the atoms attached thereto on Q5, zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E⁸ and E⁹.

For the groups represented by E¹⁰, C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and 3-fluoropropyl; and C₁-C₃ alkoxy optionally substituted with halogen may include methoxy, ethoxy, propoxy, isopropoxy, trifluoromethoxy, and difluoromethoxy.

For the groups represented by E¹¹, C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, pentafluoroethyl, and 3-fluoropropyl.

The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E¹⁰ and E¹¹ at their ends and which contains, together with the atoms attached thereto on Q6, zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E¹⁰ and E¹¹.

For the elements or groups represented by E⁴⁴, halogen may include fluorine, chlorine, bromine, or iodine; and C₁-C₃ alkyl may include methyl, ethyl, propyl, and isopropyl

For the groups represented by E¹², C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

For the groups represented by E¹³, C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

For the elements represented by E¹⁴, halogen may include chlorine, bromine, and iodine.

For the groups represented by E¹⁵, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, and amyl.

For the groups represented by E¹⁶, C₁-C₆ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, t-butyl, amyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E¹⁵ and E¹⁶ at their ends and which contains, together with the atoms attached thereto on Q9, zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include those in which tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E¹⁵ and E¹⁶.

For the groups represented by E¹⁷, E¹⁸, or E¹⁹, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.

For the groups represented by E²⁰ or E²¹, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.

For the groups represented by E²² or E²³, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, and amyl.

For the groups represented by E²⁴, C₁-C₃ alkyl may include methyl, ethyl, propyl, and isopropyl.

For the groups or elements represented by E²⁵, C₁-C₃ alkyl may include methyl, ethyl, propyl, and isopropyl; and halogen may include fluorine, chlorine, bromine, and iodine.

For the groups represented by E²⁶, C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

For the groups represented by E²⁷, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl; C₃-C₆ alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C₃-C₆ alkynyl may include propargyl, 1-methyl-2-propynyl, 2-butynyl, 3-butynyl, and 1,1-dimethyl-2-propynyl; and optionally substituted benzyl may include benzyl.

For the groups represented by E²⁸, C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl

For the groups represented by E²⁹, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl; C₃-C₆ alkenyl may include allyl, 1-methyl-2-propenyl, 3-butenyl, 2-butenyl, 3-methyl-2-butenyl, and 2-methyl-3-butenyl; C₃-C₆ alkynyl may include propargyl, 1-methyl-3-propynyl, 2-butynyl, 3-butynl, and 1,1-dimethyl-2-propynyl; and optionally substituted benzyl may include benzyl.

For the groups represented by E³⁰ or E³¹, C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

The 4- to 7-membered unsaturated ring, which is formed by combining E³⁰ and E³¹ at their ends and which contains zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene or trimethylene is formed by E³⁰ and E³¹.

For the groups represented by E⁴², C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

For the groups represented by E³², C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

For the elements or groups represented by E³³, halogen may include chlorine, bromine, and iodine; C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl and pentafluoroethyl; C₁-C₃ alkoxy optionally substituted with halogen may include methoxy and ethoxy; and C₁-C₃ alkylthio optionally substituted with halogen may include methylthio and ethylthio.

For the groups represented by E⁴³, C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

For the groups represented by E³⁴, C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

For the groups represented by E³⁵, C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

For the groups represented by E³⁶ or E³⁷, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.

The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E³⁶ and E³⁷ at their ends and which contains, together with the atoms attached thereto on Q21, zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E³⁶ and E³⁷.

For the groups represented by E³⁸, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.

For the groups represented by E³⁹, C₁-C₃ alkyl optionally substituted with halogen may include methyl, ethyl, propyl, isopropyl, trifluoromethyl, difluoromethyl, chlorodifluoromethyl, and pentafluoroethyl.

The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E³⁸ and E³⁹ at their ends and which contains, together with the atoms attached thereto on Q22, zero to two O, S, SO, SO₂ or NH groups (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E³⁸ and E³⁹.

For the groups represented by E⁴⁰, C₁-C₆ alkyl may include methyl, ethyl, propyl, isopropyl, isobutyl, butyl, isoamyl, pentyl, and hexyl.

For the groups represented by E⁴¹, C₁-C₃ alkyl may include methyl, ethyl, propyl, and isopropyl; and C₃-C₆ cycloalkyl may include cyclopropyl, cyclopentyl, and cyclohexyl.

The 4- to 7-membered saturated or unsaturated ring, which is formed by combining E⁴⁰ and E⁴¹ at their ends and which contains, together with the atoms attached thereto on Q23 (which ring may optionally be substituted with methyl or halogen), may include the cases where tetramethylene, trimethylene, or 2,2-dimethyltrimethylene is formed by E⁴⁰ and E⁴¹.

For the present compounds, there may exist geometrical isomers based on the presence of a double bond, or optical isomers and diastereomers based on the presence of at least one asymmetric carbon atom, and all of these isomers and their mixtures are also included within the scope of the present invention.

The preferred substituents from the viewpoint of herbicidal activity may include CH, CCH₃, CCl, CBr and N, more preferably CH and N, for A, and Q1, Q2, Q4, Q6, Q14, Q16, Q18, Q19 and Q20 for Q.

When Q is Q1, compounds in which E¹ and E² are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered unsaturated ring are preferred, and in particular; compounds in which the unsaturated ring is a 6-membered ring are more preferred.

When Q is Q2, compounds in which E³ and E⁴ are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring and D¹ and D² are oxygen are more preferred.

When Q is Q4, compounds in which E⁶ is C₁-C₆ alkyl optionally substituted with halogen and E⁷ is C-C₆ alkyl optionally substituted with halogen are preferred, and in particular, compounds in which E⁶ is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) and E⁷ is methyl or ethyl are more preferred. In addition, compounds in which E⁶ and E⁷ are combined at their ends to form, together with the atoms attached thereto, a 5- or 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring are more preferred.

When Q is Q6, compounds in which E¹⁰ is C₁-C₆ alkyl optionally substituted with halogen, E¹¹ is C₁-C₆ alkyl optionally substituted with halogen, and E⁴⁴ is chlorine or bromine are preferred, and in particular, compounds in which E¹⁰ is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) and E¹¹ is methyl or ethyl are more preferred. In addition, compounds in which E¹⁰ and E¹¹ are combined at their ends to form, together with the atoms attached thereto, a 5- to 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 6-membered ring are more preferred.

When Q is Q14, compounds in which D⁷ is oxygen, E²⁵ is hydrogen, E²⁶ is C₁-C₃ alkyl optionally with halogen, and E²⁷ is C₁-C₃ alkyl are preferred, and in particular, compounds in which E²⁶ is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) and E²⁷ is methyl or ethyl are more preferred.

When Q is Q16, compounds in which E³⁰ is C₁-C₃ alkyl optionally substituted with halogen, E³¹ is hydrogen or C₁-C₃ alkyl, and E⁴² is hydrogen or C₁-C₃ alkyl are preferred, and in particular, compounds in which E³⁰ is methyl, methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl), or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl), E³¹ is hydrogen or methyl, and E⁴² is hydrogen or methyl are more preferred. In addition, compounds in which E³⁰ and E³¹ are combined at their ends to form, together with the atoms attached thereto, a 5- or 7-membered saturated or unsaturated ring are preferred, and in particular, compounds in which the saturated or unsaturated ring is a 5- or 6-membered ring are more preferred.

When Q is Q18, compounds in which E³⁴ is C₁-C₃ alkyl optionally substituted with halogen are preferred, and in particular, compounds in which E³⁴ is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) are more preferred.

When Q is Q19, compounds in which V¹ is —CH₂— or —CH₂—CH₂— are preferred.

When Q is Q20, compounds in which E³⁵ is C₁-C₃ alkyl optionally substituted with halogen, Z² is nitrogen, and V² is —CH₂—CH₂— or —CH═CH— are preferred, and in particular, compounds in which E³⁵ is methyl substituted with fluorine (e.g., trifluoromethyl, chlorodifluoromethyl, difluoromethyl) or ethyl substituted with fluorine (e.g., pentafluoroethyl, 1,1-difluoroethyl) are more preferred.

Specific examples of the preferred compounds are recited below:

Methyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

Ethyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

Isopropyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetraydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

Methyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2 3,6-tetrahydropyrimidin-1-yl]-6-nitrobenzo[b]furan-5-carboxylate;

Ethyl 3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-6-nitrobenzo[b]furan-5-carboxylate;

Methyl 6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

Ethyl 6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

Methyl 7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

Ethyl 7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-carboxylate;

3-(5-Methoxybenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-(5-Methoxy-6-nitrobenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-(6-Chloro-5-methoxybenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-(7-Chloro-5-methoxybenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-[5-(Allyloxy)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-[5-(Allyloxy)-6-nitrobenzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-[5-(Allyloxy)-6-chlorobenzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-[5-(Allyloxy)-7-chlorobenzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

1-Methyl-3-[5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-6-(trifluoroethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

1-Methyl-3-[6-nitro-5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-[6-Chloro-5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-[7-Chloro-5-(prop-2-ynyloxy)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

Ethyl 2-({3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;

Ethyl 2-({6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;

Ethyl 2-({7-chloro-3-[3-methyl-2,6-dioxo-4-(trifuoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}oxy)propanoate;

1-Methyl-3-[5-(methylthio)benzo[b]furan-3-yl]-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

1-Methyl-3-[5-(methylthio)-6-nitrobenzo[b]furan-3-yl]-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-[6-Chloro-5-(methylthio)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-[7-Chloro-5-(methylthio)benzo[b]furan-3-yl]-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

Ethyl 2-({3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]-6-nitrobenzo[b]furan-5-yl}thio)propanoate;

Ethyl 2-({6-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidim-1-yl]benzo[b]furan-5-yl}thio)propanoate;

Ethyl 2-({7-chloro-3-[3-methyl-2,6-dioxo-4-(trifluoromethyl)-1,2,3,6-tetrahydropyrimidin-1-yl]benzo[b]furan-5-yl}thio)propanoate;

3-(5,7-Dichlorobenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione;

3-(5-Bromo-7-chlorobenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione; and

3-(7-Chloro-5-methylbenzo[b]furan-3-yl)-1-methyl-6-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione.

The present compounds can be produced, for example, by Producing Processes 1 to 27 as described below.

PRODUCING PROCESS 1

In the process, compound a-1 of the general formula:

wherein T, A, Y, R¹, R², R³, and R⁴ are as defined above, is reacted with acid anhydride a-5 of the general formula:

wherein E¹ and E² are as defined above.

The reaction is carried out without solvent or in a solvent. The reaction temperature is usually in the range of 50° C. to 200° C. The reaction time is usually in the range of 1 to 100 hours. The amounts of reagents to be used in the reaction are 1 mole of acid anhydride a-5 relative to 1 mole of compound a-1, which is the stoichiometric ratio but can be freely changed depending upon the reaction conditions.

The solvent which can be used may include aliphatic hydrocarbons such as hexane, heptane, octane, and ligroin; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, and mesitylene; halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, and trichlorobenzene; ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl t-butyl ether; nitro compounds such as nitromethane and nitrobenzene; organic acids such as acetic acid and propionic acid; acid amides such as N,N-dimethylformamide; sulfur compounds such as dimethylsulfoxide and sulforane; and mixtures thereof. In addition, acids such as p-toluenesulfonic acid can also be used as a reaction catalyst.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography. (see JP-A 55-139359.)

PRODUCING PROCESS 2

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, D¹, D², E³, E⁴, T, A, and Y are as defined above, R²⁰⁰ is C₁-C₅ alkyl (e.g., methyl, ethyl) or hydrogen.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-27985, or for example, by the following processes.

1). Process of Producing Compound a-2 from Compound a-1

Compound a-2 can be produced by converting compound a-1 into an isocyanate or isothiocyanate derivative in a solvent or without solvent.

Agent for conversion into isocyanate or isothiocyanate derivatives: phosgene, trichloromethyl chloroformate, oxalyl chloride, thiophosgene, etc.

Amount of agent for conversion into isocyanate or isothiocyanate derivatives: 1 equivalent to an excess amount relative to 1 mole of compound a-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.

Reaction temperature: room temperature to the reflux temperature of the agent for conversion into isocyanate or isothiocyanate derivatives

Reaction time: a moment to 48 hours.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound a-3 from Compound a-2

Compound a-3 can be produced by reacting compound a-2 with compound a-6 of the general formula:

wherein D¹, E³, E⁴, and R²⁰⁰ are as defined above, in a solvent in the presence of a base.

Amount of compound a-6: 1 to 5 moles relative to 1 mole of compound a-2

Kind of base: inorganic bases such as sodium hydride and potassium carbonate; organic bases such as triethylamine; metal alcoholates such as sodium methylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-2

Solvents: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol; and mixtures thereof; etc.

Reaction temperature: −15° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound a-4 may be directly obtained depending upon the reaction conditions of this process.

3) Process of Producing Compound a-4 from Compound a-3

Compound a-4 can be produced by reacting compound a-3 in a solvent in the presence of a base.

Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate; etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound a-3

Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as methanol and ethanol; and mixtures thereof; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 3

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, R²⁰⁰, D¹, D², E³, E⁴, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-27985, or for example, by the following processes.

1) Process of Producing Compound b-3 from Compound a-2

Compound b-3 can be produced by reacting compound a-2 with compound b-5 of the general formula:

wherein D¹, E³, E⁴, and R²⁰⁰ are as defined above, in a solvent in the presence of a base.

Amount of compound b-5: 1 to 5 moles relative to 1 mole of compound a-2

Kind of base: inorganic bases such as sodium hydride and potassium carbonate; organic bases such as triethylamine; metal alcoholates such as sodium methylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-2

Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol; and mixtures thereof; etc.

Reaction temperature: −15° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound b-4 may be directly obtained depending upon the reaction conditions of this process.

2) Process of Producing Compound b-4 from Compound b-3

Compound b-4 can be produced by reacting compound b-3 in a solvent in the presence of a base.

Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate; etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound b-3

Solvent: ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as methanol and ethanol; and mixtures thereof; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 4

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, D³, E⁵, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in WO87/03873, or for example, by the following processes.

1) Process of Producing Compound c-1 from Compound a-1

Compound c-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

2) Process of Producing Compound c-2 from Compound c-1

Compound c-2 can be produced by reacting compound c-1 and trimethylsilyl azide in a solvent or without solvent.

Amount of trimethylsilyl azide: 1 to 3 moles relative to 1 mole of compound c-1

Solvent: benzene, toluene, chlorobenzene, etc.

Reaction temperature: room temperature to the reflux temperature

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound c-3 from Compound c-2

Compound c-3 can be produced by reacting compound c-2 and compound c-4 of the general formula:

M¹—E⁵  c-4

wherein E⁵ is as defined above and M¹ is chlorine, bromine, iodine, or methanesulfonyloxy, in a solvent in the presence of a base.

Amount of compound c-4: 1 to 3 moles relative to 1 mole of compound c-2

Kind of base: sodium hydride, potassium carbonate, etc.

Amount of base: 1 to 10 moles relative to 1 mole of compound c-2

Solvent: N,N-dimethylformamide, tetrahydrofuran, etc.

Reaction temperature: room temperature to 150° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 5

This is the producing process according to the following scheme:

wherein R²⁰¹ is methoxy, ethoxy or dimethylamino; and R¹, R², R³, R⁴, E⁶, E⁷, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-149571, or for example, by the following processes.

1) Process of Producing Compound d-1 from Compound a-1

Compound d-1 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with a reducing agent such as tin (II) chloride. (see Organic Synthesis Collective Volume 1, p. 442.)

(Diazonium Salt Formation)

Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1

Kind of acid: hydrochloric acid etc.

Amount of acid: 1 mole to an excess amount relative to 1 mole of compound a-1

Solvent: water, ethanol, hydrochloric acid, etc.

Reaction temperature: −15° C. to room temperature

Reaction time: a moment to 24 hours

(Reduction Reaction)

Kind of reducing agent: tin (II) chloride etc.

Amount of reducing agent: 3 to 10 moles relative to 1 mole of compound a-1

Solvent: hydrochloric acid etc.

Reaction temperature: −15° C. to room temperature

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound d-3 from Compound d-1

Compound d-3 can be produced by reacting compound d-1 and compound d-5 of the general formula:

wherein E⁷ and R²⁰¹ are as defined above and R²⁰² is methyl or ethyl, in a solvent, if necessary, in the presence of a base, to give intermediate d-2 and then reacting the intermediate d-2 in the presence of a base.

Intermediate d-2 may be isolated.

(Reaction of Compound d-1 into Compound d-2)

Amount of compound d-5: 1 to 3 moles relative to 1 mole of compound d-1.

Kind of base: organic bases such as triethylamine and pyridine; metal alcoholates such as sodium methylate and sodium ethylate; inorganic bases such as sodium hydroxide and potassium carbonate; etc.

Solvent: aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol and isopropanol; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

(Reaction of Compound d-2 into Compound d-3)

Kind of base: organic bases such as triethylamine and pyridine; metal alcoholates such as sodium methylate and sodium ethylate; inorganic bases such as sodium hydroxide and potassium carbonate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound a-1

Solvent: aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated aromatic hydrocarbons such as chlorobenzene; alcohols such as ethanol and isopropanol; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran and 1,4-dioxane; etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound d-4 from Compound d-3

Compound d-4 can be produced by reacting compound d-3 with compound d-6 of the general formula:

M¹—E⁶  d-6

wherein E⁶ and M¹ are as defined above, in a solvent in the presence of a base.

Amount of compound d-6: 1 to 3 moles relative to 1 mole of compound d-3

Kind of base: sodium hydride, potassium carbonate, etc.

Amount of base: 1 to 10 moles relative to 1 mole of compound d-3

Solvent: N,N-dimethylformamide, tetrahydrofuran, etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound d-3 can also be produced according to the following scheme. (see JP-A 7-503253.)

wherein R¹, R², R³, R⁴, E⁷, T, A, and Y are as defined above.

1) Process of Producing Compound e-1 from Compound d-1

Compound e-1 can be produced by reacting compound d-1 with compound e-3 of the general formula:

wherein E⁷ is as defined above, in a solvent.

Amount of compound e-3: 1 to 10 moles relative to 1 mole of compound d-3

Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.

Reaction temperature: −15° C. to 70° C.

Reaction time: a moment to 24 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound e-1 can also be used as such for the reaction in the next step without isolation.

2) Process of Producing Compound e-2 from Compound e-1

Compound e-2 can be produced by reacting compound e-1 with an alkali metal cyanate, in a solvent, if necessary, in the presence of an acid.

Kind of alkali metal cyanate: NaOCN, KOCN, etc.

Amount of alkali metal cyanate: 1 to 3 moles relative to 1 mole of compound e-1

Kind of acid: organic acids such as acetic acid

Amount of acid: 0.01 to 1 mole relative to 1 mole of compound e-1

Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.

Reaction temperature: −15° C. to 80° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallzation or column chromatography.

Compound e-2 can also be used as such in the next step without isolation.

3) Process of Producing Compound d-3 from Compound e-2

Compound d-3 can be produced by oxidizing compound e-2 with an oxidizing agent such as halogen, hypohalous acid, or hypohalite in a solvent.

Kind of oxidizing agent: chlorine, hypochlorous acid, sodium hypochlorite, etc.

Amount of oxidizing agent: 1 to 3 moles relative to 1 mole of compound e-2

Solvent: water; alcohols such as ethanol and t-butanol; and mixtures thereof; etc.

Reaction temperature: −15° C. to 60° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example; the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 6

This is the producing process according to the following scheme:

wherein R¹, R¹, R³, R⁴, E¹⁰, E¹¹, T, A, and Y are as defined above; E¹⁴⁴ is halogen; and R²⁰³ is methyl or ethyl.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-233061, or for example, by the following processes.

1) Process of Producing Compound f-2 from Compound d-1

Compound f-2 can be produced by reacting compound d-1 with compound f-4 of the general formula:

wherein E¹⁰, E¹¹, and R²⁰³ are as defined above, in a solvent, if necessary, in the presence of an acid.

Amount of compound f-4: 1 to 10 moles relative to 1 mole of compound d-1

Solvent: water; alcohols such as ethanol, isopropanol and butanol; aromatic hydrocarbons such as benzene and toluene; organic acids such as acetic acid and propionic acid; and mixtures thereof; etc.

Kind of acid: p-toluenesulfonic acid, hydrochloric acid, acetic acid, etc.

Amount of acid: 0.0001 mole to an excess amount relative to 1 mole of compound d-1

Reaction temperature: room temperature to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound f-3 from Compound f-2

Compound f-3 can be produced by reacting compound f-2 with a halogenating agent in a solvent or without solvent under normal pressure or increased pressure.

Kind of halogenating agent: phosphorous oxychloride, phosphorous pentachloride, oxalyl chloride, phosgene, trichloromethyl chloroformate, etc.

Amount of halogenating agent: 1 mole to an excess amount relative to 1 mole of compound f-2

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.

Reaction temperature: 50° C. to 250° C.

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

The compounds wherein E¹⁰ is CF₂H can also be produced according to the following scheme:

wherein R¹, R², R³, R⁴, E¹¹, E¹⁴⁴, T, A, and Y are defined above.

1) Process of Producing Compound g-2 from Compound g-1

Compound g-2 can be produced by reacting compound g-1 with a Vilsmeier reagent (prepared from dimethylformamide and a halide such as phosphorus oxychloride, phosphorus pentachloride, oxalyl chloride, phosgene or trichloromethyl chloroformate; see Jikken Kagaku Koza, 4th Edition, 21, p. 110) in a solvent or without solvent.

Amount of Vilsmeier reagent: 1 to 20 moles relative to 1 mole of compound g-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: −10° C. to 150° C.

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaing the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound g-3 from Compound g-2

Compound g-3 can be produced by reacting compound g-2 with a fluorinating agent in a solvent.

Kind of fluorinating agent: dimethylaminosulfur trifluoride etc.

Amount of fluorinating agent: 1 to 10 moles relative to 1 mole of compound g-2

Solvent: halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: −10° C. to room temperature

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 7

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E¹², D⁴, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-109578, or for example, by the following processes.

1) Process of Producing Compound h-1 from Compound d-1

Compound h-1 can be produced by reacting compound d-1 with an acylating agent selected from compound h-3 of the general formula:

wherein E¹² is as defined above and R²⁰⁴ is hydrogen, methyl, or ethyl, compound h-4 of the general formula:

wherein E¹² is as defined above, and compound h-5 of the general formula:

wherein E¹² is as defined above, in a solvent or without solvent.

Amount of acylating agent: 1 to 5 moles relative to 1 mole of compound d-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound h-2 from Compound h-1

Compound h-2 can be produced by reacting compound h-1 with compound h-6 of the general formula:

wherein D⁴ is as defined above, in a solvent in the presence of a base.

Amount of compound h-6: 1 to 5 moles of compound h-1

Kind of base: organic bases such as ti4triethylamine and pyridine; inorganic bases such as potassium carbonate; etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound h-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: −10° C. to room temperature

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 8

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E¹³, T, A, and Y are as defined above; E¹¹⁴ is halogen; and R²⁰⁵ is methyl or ethyl.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-145011, or for example, by the following processes.

1) Process of Producing Compound i-1 from Compound a-1

Compound i-1 can be produced by reacting compound a-1 with a chloroformate i-5 of the general formula:

ClCOOR²⁰⁵  i-5

wherein R²⁰⁵ is as defined above, in a solvent in the presence of a base.

Amount of chloroformate i-5: 1 to 10 moles relative to 1 mole of compound a-1

Kind of base: N,N-dimethylaniline, N,N-diethylaniline, etc.

Amount of base: 1 to 10 moles relative to 1 mole of compound a-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: room temperature to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound i-2 from Compound i-1

Compound i-2 can be produced by reacting compound i-1 with compound i-6 of the general formula:

wherein E¹³ is as defined above and M⁶ is chlorine or bromine, in a solvent in the presence of lithium bis(trimethylsilyl)amide.

Amount of compound i-6: 1 to 10 moles relative to 1 mole of compound i-1

Amount of lithium bis(trimethylsilyl)amide: 1 to 10 moles relative to 1 mole of compound i-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: room temperature to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound i-3 from Compound i-2

Compound i-3 can be produced by reacting compound i-2 with a halogenating agent in a solvent.

Kind of halogenating agent: chlorine, bromine, etc.

Amount of halogenating agent: 1 mole to large excess relative to 1 mole of compound i-2

Solvent: halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: 10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound i-4 from Compound i-3

Compound i-4 can be produced by reacting compound i-3 with a base in a solvent.

Kind of base: organic bases such as triethyl amine and 1,8-diazabicylo[5.4.0]undec-7-ene; etc.

Amount of base: 1 mole to large excess relative to 1 mole of compound i-3

Solvent: dimethylsulfoxide etc.

Reaction temperature: 10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 9

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E¹⁵, E¹⁶, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 60-104073, or for example, by the following processes.

1) Process of Producing Compound j-1 from Compound d-1

Compound j-1 can be produced by reacting compound d-1 with compound j-3 of the general formula:

wherein E¹⁵ and E¹⁶ are as defined above, in a solvent, if necessary, in the presence of an acid.

Amount of compound j-3: 1 to 5 moles relative to 1 mole of compound d-1

Solvent: toluene, ethanol, acetic acid, tetrahydrofuran, etc.

Acid: p-toluenesulfonic acid etc.

Reaction temperature: −10° C. to 100° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound j-2 from Compound j-1

Compound j-2 can be produced by reacting compound j-1 with an oxidizing agent in a solvent in the presence of a pyridine.

Amount of pyridine: 1 to 2 moles relative to 1 mole of compound j-1

Kind of oxidizing agent: copper (II) sulfate etc.

Amount of oxidizing agent: 1 to 5 moles relative to 1 mole of compound j-1

Solvent: toluene, ethanol, acetic acid, tetrahydrofuran, etc.

Reaction temperature: −10° C. to 100° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 10

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E¹⁷, E¹⁸, E¹⁹, D⁵, T, A, and Y are as defined above and R²⁰⁶ is methyl or ethyl.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-183567, or for example, by the following processes.

1) Process of Producing Compound k-1 from Compound a-1

Compound k-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

2) Process of Producing Compound k-2 from Compound k-1

Compound k-2 can be produced by reacting compound k-1 with compound k-5 of the general formula:

wherein E¹⁸, E¹⁹, and R²⁰⁶ are as defined above, in a solvent in the presence of a base.

Amount of compound k-5: 1 to 2 moles relative to 1 mole of compound k-1

Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound k-1

Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

Reaction temperature: −10° C. to 100° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound k-3 may be obtained directly depending upon the reaction conditions of this process.

3) Process of Producing Compound k-3 from Compound k-2

Compound k-3 can be produced by reacting compound k-2 in a solvent in the presence of a base.

Kind of base: potassium carbonate, sodium hydride, sodium methylate, etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound k-2

Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

Reaction temperature: −10° C. to 100° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound k-4 from Compound k-3

Compound k-4 can be produced by reacting compound k-3 with compound k-6 of the general formula:

M⁷—E¹⁷  k-6

wherein E⁷ is as defined above and M⁷ is iodine, bromine, or chlorine, in a solvent in the presence of a base.

Amount of compound k-6: 1 to 2 molesrelative to 1 mole of compound k-3

Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound k-3

Solvent: toluene, ethanol, tetrahydrofuran, N,N-diinethylformamide, etc.

Reaction temperature: −10° C. to 100° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to ost-treatments, for example, the reaction mixture is poured into water, and he deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaiing the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 11

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E²⁰, E²¹, D⁶, T, A, and Y are as defined above and R²⁰⁷ is methyl or ethyl.

The reactions in the respective steps can be carried out, for example, according to the processes as described in WO87/62357, or for example, by the following processes.

1) Process of Producing Compound l-1 from Compound a-1

Compound l-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

2) Process of Producing Compound l-2 from Compound l-1

Compound l-2 can be produced by reacting compound l-1 with compound l-4 of the general formula.

wherein E²⁰, E²¹, and R²⁰⁷ are as defined above, in a solvent in the presence of a base.

Amount of compound l-4: 1 to 2 moles relative to 1 mole of compound l-1

Kind of base: triethylamine, potassium carbonate, sodium hydride, sodium methylate, etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound l-1

Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

Reaction temperature: −10° C. to 100° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound l-3 may be obtained directly depending upon the reaction conditions of this process.

3) Process of Producing Compound l-3 from Compound l-2

Compound l-3 can be produced by reacting compound l-2 in a solvent in the presence of a base.

Kind of base: potassium carbonate, sodium hydride, sodium methylate, etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound l-2

Solvent: toluene, ethanol, tetrahydrofuran, N,N-dimethylformamide, etc.

Reaction temperature: −10° C. to 100° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 12

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E²², E²³, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 61-103801, or for example, by the following processes.

1) Process of Producing Compound m-1 from Compound a-1

Compound m-1 can be produced by reacting compound a-1 with acid anhydride m-2 of the general formula:

wherein E²² and E²³ are as defined above, usually without solvent, or in a solvent, if necessary, in the presence of an acid.

The reaction temperature is usually in the range of 50° C. to 200° C. The reaction time is usually in the range of 1 to 100 hours. The amounts of agents to be used in the reaction are 1 mole of acid anhydride m-2 relative to 1 mole of compound a-1, which; is the stoichiometric ratio but can be freely changed depending upon the reaction conditions.

The solvent which can be used may include aliphatic hydrocarbons such as hexane, heptane, octane, and ligroin; aromatic hydrocarbons such as benzene, toluene, ethylbenzene, xylene, and mesitylene; halogenated hydrocarbons such as chlorobenzene, dichlorobenzene, and trichlorobenzene; ethers such as 1,4-dioxane, tetrahydrofuran, ethylene glycol dimethyl ether, and methyl t-butyl ether; nitro compounds such as nitromethane and nitrobenzene; organic acids such as acetic acid and propionic acid; acid amides such as N,N-dimethylformamide; sulfur compounds such as dimethylsulfoxide and sulforane; and mixtures thereof As the acid, p-toluenesulfonic acid can be used.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 13

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E²⁴, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in WO86/00072, or for example, by the following processes.

1) Process of Producing Compound n-1 from Compound a-1

Compound n-1 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in a solvent in the presence of an acid and then reacting the diazonium salt with compound n-5 of the formula:

in a solvent in the presence of a base.

(Diazonium salt formation)

Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1

Kind of acid: hydrochloric acid etc.

Amount of acid: 1 mole to an excess amount relative to 1 mole of compound a-1

Solvent: water, ethanol, hydrochloric acid, etc.

Reaction temperature: −15° C. to room temperature

Reaction time: a moment to 24 hours

(Reaction with compound n-5)

Amount of compound n-5: 1 to 5 moles relative to 1 mole of compound a-1

Kind of base: sodium acetate etc.

Amount of base: 0.8 to 3 moles relative to 1 mole of acid used in the forgoing step

Solvent: ethanol, water, etc.

Reaction temperature: 0°C. to 60° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound n-2 from Compound n-1

Compound n-2 can be produced by reacting compound n-1 in a solvent in the presence of a base.

Kind of base: sodium hydroxide, potassium hydroxide, etc.

Amount of base: 1 to 10 moles relative to 1 mole of compound n-1

Solvent: ethanol, N,N-dimethylformamide, water, and mixtures thereof; etc.

Reaction temperature: 0° C. to 110° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound n-3 from Compound n-2

Compound n-3 can be produced by reacting compound n-2 in a solvent in the presence of thioacetic acid.

Amount of thioacetic acid: 0.1 to 10 moles relative to 1 mole of compound n-2

Solvent: xylene etc.

Reaction temperature: reflux temperature

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound n-4 from Compound n-3

Compound n-4 can be produced by reacting compound n-3 with compound n-6 of the general formula:

M⁸—E²⁴  n-6

wherein E²⁴ is as defined above and M⁸ is iodine, bromine, or chlorine, in a solvent in the presence of a base.

Amount of compound n-6: 1 to 10 moles relative to 1 mole of compound n-3

Kind of base: potassium carbonate, sodium hydride, etc.

Amount of base: 1 to 10 moles relative to 1 mole of compound n-3

Solvent: acetone, tetrahydrofuran, N,N-dimethylformamide, etc.

Reaction temperature: 0° C. to 100° C.

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 14

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E²⁵, E²⁶, E²⁷, T, A, and Y are as defined above, and R²⁰⁸ and R²⁰⁹ are independently C₁-C₅ alkyl (e.g., methyl, ethyl, propyl).

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 5-4959 and JP-A 63-41466, or for example, by the following processes.

1) Process of Producing Compound o-1 from Compound a-1

Compound o-1 can be produced from compound a-1 and chloroformate o-4 of the general formula:

ClCOOR²⁰⁸  o-4

wherein R²⁰⁸ is as defined above, according to the process as described above in Producing Process 8, Step 1).

2) Process of Producing Compound o-11from Compound o-1

Compound o-11 can be produced by reacting compound o-1 with compound o-5 of the general formula:

wherein E²⁵, E²⁶, and R²⁰⁹are as defined above, in a solvent in the presence of a base.

Amount of compound o-5: 0.9 to 10 moles relative to 1 mole of compound o-1

Kind of base: inorganic bases such as sodium hydride; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound o-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.

Reaction temperature: room temperature to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound o-11can also be used as such for the reaction in the next step without isolation.

3) Process of Producing Compound o-2 from Compound o-11

Compound o-2 can be produced by reacting compound o-11 in a solvent in the presence of a base.

Kind of base: inorganic bases such as sodium hydride and potassium carbonate; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10moles relative to 1 mole of compound o-11

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; sulfur compound such as dimethylsulfoxide; and mixtures thereof

Reaction temperature: room temperature to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound o-2 can also be used as such for the reaction in the next step without isolation.

4) Process of Producing Compound o-3 from Compound o-2

Compound o-3 can be produced by reacting compound o-2 with compound o-6 of the general formula:

M⁹—E²⁷  o-6

wherein E²⁷ is as defined above and M⁹ is iodine, bromine, chlorine, methanesulfonyloxy, or 2,4-dinitrophenoxy, in a solvent in the presence of a base.

Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound o-2

Kind of base: inorganic bases such as sodium hydride, potassium carbonate, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound o-2

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 15

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, D⁷, E²⁵, E²⁶, E²⁷, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-41466, or for example, by the following processes.

1) Process of Producing Compound p-1 from Compound a-1

Compound p-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

2) Process of Producing Compound p-2 from Compound p-1

Compound p-2 can be produced by reacting compound p-1 with compound p-7 of the general formula:

wherein E²⁵, E²⁶, and R²⁰⁹ are as defined above, in a solvent in the presence of a base.

Amount of compound p7: 0.9 to 10 moles relative to 1 mole of compound p-1

Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.

Reaction temperature: −40° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound p-2 can also be used as such for the reaction in the next step without isolation.

3) Process of Producing Compound p-3 from Compound p-2

Compound p-3 can be produced by reacting compound p-2 with compound o-6 of the general formula:

M⁹—E²⁷  o-6

wherein E²⁷ and M⁹ are as defined above, in a solvent in the presence of a base.

Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound p-2

Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-2

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 16

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, D⁷, E²⁵, E²⁶, E²⁷, T, A, and Y as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 63-41466, or for example, by the following processes.

1) Process of Producing Compound p-4 from Compound p-1

Compound p-4 can be produced by reacting compound p-1 with ammonia in a solvent.

Amount of ammonia: 1 mole to large excess relative to 1 mole of compound p-1

Solvent: water, methanol, ethanol, tetrahydrofuran, 1,4-dioxane, etc.

Reaction temperature: −20° C. to 100° C.

Reaction time: a moment to 24 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound p-2 from Compound p-4

Compound p-2 can be produced by reacting compound p-4 with compound p-9 of the general formula:

wherein E²⁵, E²⁶, and R²⁰⁹ are as defined above and R²¹⁰ is methyl, in a solvent in the presence of a base.

Amount of compound p-9: 0.9 to 10 moles relative to 1 mole of compound p-4

Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-4

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: room temperature to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound p-2 can also be used as such for the reaction in the next step without isolation.

3) Process of Producing Compound p-3 from Compound p-2

Compound p-3 can be produced by reacting compound p-2 with compound o-6 of the general formula:

M⁹—E²⁷  o-6

wherein E²⁷ and M⁹ are as defined above, in a solvent in the presence of a base.

Amount of compound o-6: 0.9 to 10 moles relative to 1 mole of compound p-2

Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound p-2

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 17

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, D⁷, E²⁸, E²⁹, A, T, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-92943, or for example, by the following processes.

1) Process of Producing Compound p-6 from Compound p-5

Compound p-6 can be produced by reducing compound p-5 in a solvent.

Kind of reducing agent: NaBH₄ etc.

Amount of reducing agent: 1 to 10 moles relative to 1 mole of compound p-5

Solvent: water, methanol, ethanol, acetic acid, etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 18

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E³⁰, E³¹, E⁴², T, A, and Y are as defined above, and R²¹¹ is hydrogen, methyl, or ethyl.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 9-323977 and WO98/17632, or for example, by the following processes.

1) Process of Producing Compound w-1 from Compound a-1

Compound w-1 can be produced from compound a-1 according to the process as described above in Producing Process 5, Step 1).

2) Process of Producing Compound w-2 from Compound w-1

Compound w-2 can be produced by reacting compound w-8 of the general formula:

wherein E³⁰ and E⁴² are as defined above and M¹⁰ is iodine, bromine, or chlorine, with water in the presence of a base to form compound w-9 of the general formula:

wherein E³⁰ and E⁴² are as defined above (reaction 1), and then reacting the carbonyl derivative with compound w-1 (reaction 2).

(Reaction 1)

Reaction 1 is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 100° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 2 moles of each of the water and base relative to 1 mole compound w-8, which is ideal but can be freely changed depending upon the reaction conditions.

As the base to be used, both organic bases and inorganic bases can be used, examples of which are sodium acetate and potassium acetate.

The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof

(Reaction 2)

Reaction 2 is usually carried out in a solvent. The reaction temperature is usually in the range of −20° C. to 200° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of compound w-1 relative to 1 mole of compound w-8, which is ideal but can be freely changed depending upon the reaction conditions. Depending upon the conditions, salts of compound w-1, such as hydrochloride salt and sulfate salt, can also be used.

The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound w-3 from Compound w-2 (Route 1)

Compound w-3 can be produced by reacting compound w-2 with phosphorane compound w-10 of the general formula:

wherein E³¹ is as defined above; R²¹³ is methyl or ethyl; and Ar is optionally substituted phenyl (e.g., phenyl), in a solvent.

This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of −20° C. to 150° C, preferably 0° C. to 100° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of compound w-10 relative to 1 mole of compound w-2, which is ideal but can be freely changed depending upon the reaction conditions.

The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound w-4 from Compound w-2 (Route 2)

Compound w-4 can be produced by reacting compound w-2 with compound w-11 of the general formula:

wherein E³¹ and R²¹¹ are as defined above, in the presence of a base.

This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 200° C., preferably 40° C. to 150° C. The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are usually 1 to 10 moles of compound w-11, preferably 1 to 2 moles of compound w-11, which is ideal, relative to 1 mole of compound w-2. The amount of base is usually 1 mole to large excess, preferably 1 to 10 moles, relative to 1 mole of compound w-11

The base which can be used may include organic bases such as triethylamine and tributylamine.

The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining he desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

5) Process of Producing Compound w-3 from Compound w-4

Compound w-3 can be produced by reacting compound w-4, if necessary, in the presence of a base or acid, or in an acid-base mixed system.

This reaction is usually carried out in a solvent. The reaction temperature is usually in the range of 20° C. to 200° C., preferably 40° C. to 150° C. The reaction time is usually in the range of a moment to 96 hours.

The kind of base used, if necessary, may include organic bases such as pyridine; and metal alcoholates such as sodium methylate. The amount of base is usually 1 mole to large excess, preferably 1 to 10 moles, which is ideal, relative to 1 mole of compound w-4.

The kind of add used, if necessary, may include organic acids such as acetic acid and benzoic acid; and p-toluenesulfonic acid. The amount of acid is usually 1 mole to large excess, preferably 1 to 10 moles, which is ideal, relative to 1 mole of compound w-4.

The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; esters such as ethyl acetate and butyl acetate; nitro compounds such as nitromethane and nitrobenzene; nitrites such as acetonitrile; amides such as N,N-di-methylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound w-7 (i.e., compound w-2 wherein E⁴² is H) can also be produced according to the following scheme:

wherein R¹, R², R³, R⁴, E³⁰, T, A, and Y are as defined above, and R²¹⁴ is methyl or ethyl.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 9-323977, or for example, by the following processes.

6) Process of Producing Compound w-5 from Compound a-1 (see Tetrahedron, vol. 35, p. 2013 (1979))

Compound w-5 can be produced by converting compound a-1 into a diazonium salt with sodium nitrite in a solvent in the presence of an acid, and then reacting the diazonium salt with compound w-12 of the general formula:

wherein E³⁰ and R²¹⁴ are as defined above, in a solvent in the presence of a base.

(Diazonium salt formation)

Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound a-1

Kind of acid: hydrochloric acid etc.

Amount of acid: 1 to 100 moles relative to 1 mole of compound a-1

Solvent: water, ethanol, hydrochloric acid, etc.

Reaction temperature: −15° C. to room temperature

Reaction time: a moment to 24 hours

(Reaction with compound w-12)

Amount of compound w-12: 1 to 5 moles relative to 1 mole of compound a-1

Kind of base: sodium acetate etc.

Amount of base: 0.8 to 3 moles relative to 1 mole of acid used in the forgoing step

Solvent: ethanol, water, etc.

Reaction temperature: 0° C. to 60° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

6) Process of Producing Compound w-6 from Compound w-5

Compound w-6 can be produced by reacting compound w-5 in a solvent in the presence of a base.

The reaction temperature is usually in the range of 0° C. to 150° C.

The reaction time is usually in the range of a moment to 72 hours. The amounts of agents to be used in the reaction are 1 mole of base relative to 1 mole of compound w-5, which is ideal but can be freely changed, if necessary. The base may include inorganic bases such as sodium hydroxide, lithium hydroxide, lithium hydroxide monohydrate, barium hydroxide, and potassium hydroxide.

The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; nitrites such as acetonitrile; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

7) Process of Producing Compound w-7 from Compound w-6

Compound w-7 can be produced by heating compound w-6 in a solvent.

The reaction temperature is usually in the range of 50° C. to 200° C. The reaction time is usually in the range of a moment to 72 hours.

The solvent which can be used may include aromatic hydrocarbons such as benzene, toluene, and xylene; halogenated hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; nitrites such as acetonitrile; amides such as N,N-dimethylformamride; alcohols such as methanol, ethanol and isopropanol; nitrogen-containing aromatic compounds such as pyridine and picoline; sulfur compounds such as dimethylsulfoxide; tertiary amines such as N,N-dimethylailine; water; and mixtures thereof.

In this reaction, metals such as copper powder may be used as a catalyst, if necessary.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 19

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E³², E³³, E⁴³, T, A, and Y are as described above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 6-25186, or for example, by the following processes.

1) Process of Producing Compound r-1 from Compound a-1

Compound r-1 can be produced by converting compound a-1 into an isothiocyanate derivative in a solvent or without solvent.

Agent for conversion into isothiocyanate derivatives: thiophosgene etc.

Amount of agent for conversion into isothiocyanate derivatives: 1 equivalent to an excess amount relative to 1 mole of compound a-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; etc.

Reaction temperature: room temperature to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound r-2 from Compound r-1

Compound r-2 can be produced by reacting compound r-1 with compound r-6 of the general formula:

wherein E³² and E⁴³ are as defined above and R²¹⁵ is methyl, ethyl, or propyl in a solvent in the presence of a base.

Amount of compound r-6: 0.9 to 10 moles relative to 1 mole of compound r-1

Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound r-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chrormatography.

3) Process of Producing Compound r-3 from Compound r-2

Compound r-3 can be produced by reacting compound r-2 with Raney nickel in a solvent in the presence of a base.

Amount of Raney nickel: 1 to 20 moles relative to 1 mole of compound r-2

Kind of base: nitrogen-containing compounds such as pyridine; organic bases such as triethylamine; ammonia; etc.

Amount of base: 0. 1 to 20 moles relative to compound r-2

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound r-4 from Compound r-3

Compound r-4 can be produced by reacting compound r-3 in a solvent in the presence of a base.

Kind of base: metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 1 to 20 moles relative to compound r-3

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.

Reaction temperature: 20° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

5) Process of Producing Compound r-5 from Compound r-4

Compound r-5 can be produced by reacting compound r-4 with an acylating agent selected from compound r-7 of the general formula:

wherein E³³ is as defined above, or compound r-8 of the general formula:

wherein E³³ is as defined above, in a solvent.

Amount of acylating agent: 1 to 5 moles relative to 1 mole of compound r-4

Solvent: organic acids such as acetic acid and propionic acid; etc.

Reaction temperature: the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 20

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, E³⁴, T, A, and Y are as defined above.

The reaction can be carried out, for example, according to the process as described in JP-A 4-356463, or for example, by the following process.

1) Process of Producing Compound s-1 from Compound a-1

Compound s-1 can be produced by reacting compound a-1 with acid anhydride s-2 of the general formula:

wherein E³⁴ is as defined above, in a solvent, if necessary, in the presence of an acid.

Amount of acid anhydride s-2: 1 to 5 moles relative to 1 mole of compound a-1

Solvent: organic acids such as acetic acid and propionic acid; aromatic hydrocarbons such as benzene and toluene; etc.

Kind of acid: p-toluenesulfonic acid etc.

Reaction temperature: room temperature to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 21

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, D⁹, V¹, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in JP-A 5-25173, or for example, by the following processes.

1) Process of Producing Compound t-1 from Compound a-1

Compound t-1 can be produced from compound a-1 according to the process as described above in Producing Process 2, Step 1).

2) Process of Producing Compound t-2 from Compound t-1

Compound t-2 can be produced by reacting compound t-1 with compound t-3 of the general formula:

wherein V¹ is as defined above, in a solvent in the presence of a base.

Amount of compound t-3: 0.9 to 10 moles relative to 1 mole of compound t-1

Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound t-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.

Reaction temperature: −40° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 22

This is the producing process according to the following schemes:

wherein R¹, R², R³, R⁴, E³⁵, A, T, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, according to the processes as described in WO98/14452, or for example, by the following processes.

1) Process of Producing Compound u-1 from Compound a-1

Compound u-1 can be produced from compound a-1 according to the process as described above in Producing Process 19, Step 1).

2) Process of producing compound u-2 from Compound u-1

Compound u-2 can be produced by reacting compound u-1 with compound u-12 of the general formula:

wherein E³⁵ and R²¹⁵ are as defined above, in a solvent in the presence of a base.

Amount of compound u-12: 0.9 to 10 moles relative to 1 mole of compound u-1

Kind of base: inorganic bases such as sodium hydride, potassium hydroxide, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 0.1 to 10 moles relative to 1 mole of compound u-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N,N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; and mixtures thereof; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated,. thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound u-3 from Compound u-2

Compound u-3 can be produced by reacting compound u-2 with a methylating agent such as methyl iodide or dimethyl sulfate in a solvent in the presence of a base.

Kind of base: organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; inorganic bases such as sodium hydride, potassium carbonate, and potassium hydroxide; etc.

Amount of base: 1 to 20 moles relative to 1 mole of compound u-2

Amount of methylating agent: 1 to 20 moles relative to 1 mole of compound u-2

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; water; and mixtures thereof; etc.

Reaction temperature: −10° C. to room temperature

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound u-4 from Compound u-3

Compound u-4 can be produced by reacting compound u-3 with an oxidizing agent in a solvent.

Kind of oxidizing agent: m-chloroperbenzoic acid, aqueous hydrogen peroxide, etc.

Amount of oxidizing agent: 2 to 20 moles relative to 1 mole of compound u-3

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated aliphatic hydrocarbons such as chloroform; water; and mixtures thereof; etc.

Reaction temperature: −20° C. to room temperature

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

5) Process of Producing Compound u-5 from Compound u-4

Compound u-5 can be produced by reacting compound u-4 with ammonia in a solvent.

Amount of ammonia: 1 mole to large excess relative to 1 mole of compound u-4

Solvent: t-butanol, isopropanol, etc.

Reaction temperature: −20° C. to 40° C.

Reaction time: a moment to 10 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

6) Process of Producing Compound u-6 from Compound u-4

Compound u-6 can be produced by reacting compound u-4 with an azidizing agent such as sodium azide or trimethylsilyl azide in a solvent such as methanol, ethanol, and water.

Amount of azidizing agent: 1 equivalent to an excess amount relative to 1 mole of compound u-4

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

7) Process of Producing Compound u-7 from Compound u-5

Compound u-7 can be produced by reacting compound u-5 with a haloacetaldehyde such as chloroacetaldehyde (40% aqueous solution) in a solvent.

The amount of haloacetaldehyde is 1 equivalent to an excess amount relative to 1 mole of compound u-5. The solvent may include ethers such as 1,4-dioxane and tetrahydrofuran; water; and mixtures thereof; etc. The reaction temperature is in the range of 40° C. to the reflux temperature of the solvent. The reaction time is in the range of a moment to 20 hours.

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining he desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

8) Process of Producing Compound u-8 from Compound u-4

Compound u-8 can be produced by reacting compound u-4 with hydrazine (hydrate) in a solvent or without solvent.

Amount of hydrazine: 1 mole to a large excess amount relative to 1 mole of compound u-4

Solvent: t-butanol, isopropanol, etc.

Reaction temperature: −20° C. to 40° C.

Reaction time: a moment to 10 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

9) Process of Producing Compound u-9 from Compound u-4

Compound u-9 can be produced by reacting compound u-4 with 2-ethanolamine in a solvent or without solvent.

Amount of 2-ethanolamine: 1 mole to a large excess amount relative to 1 mole of compound u-4

Solvent: t-butanol, isopropanol, etc.

Reaction temperature: −20° C. to 40° C.

Reaction time: a moment to 10 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

10) Process of Producing Compound u-10 from Compound-u-8

Compound u-10 can be produced by reacting compound u-8 with formic acid in a solvent or without solvent, if necessary, in the presence of another acid.

Kind of acid: p-toluenesulfonic acid, hydrochloric acid, etc.

Amount of acid: 0.001 mole to a large excess amount relative to 1 mole of compound u-8

Amount of formic acid: 1 mole to a large excess amount to 1 mole of compound u-8

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N-N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof, etc.

Reaction temperature: 40° C. to the reflux temperature of the solvent

Reaction time: a moment to 10 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

11) Process of Producing Compound u-11 from Compound u-9

Compound u-11 can be produced by reacting compound u-9 in a solvent or without solvent in the presence of an acid.

Kind of acid: p-toluenesulfonic acid, hydrochloric acid, sulfuric acid, polyphosphoric acid, etc.

Amount of acid: 0.001 mole to a large excess amount relative to 1 mole of compound u-9

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; amides such as N-N-dimethylformamide; ethers such as tetrahydrofuran; halogenated aliphatic hydrocarbons such as chloroform; alcohols such as methanol and ethanol; water; and mixtures thereof; etc.

Reaction temperature: 40° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 23

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, R²⁵, E³², E³³, E⁴³, T, A, and Y are as defined above; and R²¹⁶is C₁-C₆ alkoxy (e.g., methoxy, ethoxy) or NR²¹⁷(R²¹⁸ (e.g., dimethylamino, dimethylamino) wherein R²¹⁷ and R²¹⁸ are independently C₁-C₅ alkyl.

The reactions in the respective steps can be carried out, for example, according to the processes as described in Bull. Soc. Chim. Fr. (134, pp. 47-57, 1997), or for example, by the following processes.

1) Process of Producing Compound r-9 from Compound r-6

Compound r-9 can be produced by reacting compound r-6 with compound r-10 of the general formula:

wherein E³³ and R²¹⁶ are as defined above; R²¹⁹ and R²²⁰ are independently C₁-C₆ alkyl (e.g., methyl, ethyl), in a solvent, if necessary, in the presence of an acid.

Amount of compound r-10: 1 mole to an excess amount relative to 1 mole of compound r-6

Kind of acid: organic acids such as acetic acid and p-toluenesulfonic acid

Amount of acid: a catalytic amount to large excess relative to 1 mole of compound r-6

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours,

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound r-5 from Compound r-9

Compound r-5 can be produced by reacting compound r-9 with compound a-1 in a solvent, if necessary, in the presence of an acid.

Amount of compound a-1: 0.9 to 1.1 moles relative to 1 mole of compound r-9

Kind of acid: organic acids such as acetic acid and p-toluenesulfonic acid

Amount of acid: a catalytic amount to large excess relative to 1 mole of compound r-9

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Depending upon the kinds of R¹, R², R³, R⁴, Y, T, and A, the formation of Q may be followed by the introduction or formation of R¹, R², R³, R⁴, Y, T, and A. In these producing processes, protective groups may be used, if necessary, for the protection, of functional groups from the reactions. (see “Protective Groups in Organic Synthesis” written by T. W. Greene.) The following are examples of these producing processes.

PRODUCING PROCESS 24

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, Y¹¹, and Q are as defined above; R²²¹ is methoxycarbonyl, ethoxycarbonyl, propoxycarbonyl, isopropoxycarbonyl, aminocarbonyl, or nitrile; and M²³ is fluorine, chlorine, or bromine.

The reactions in the respective steps can be carried out, for example, by the following processes.

1) Process of Producing Compound z-2 from Compound z-1

Compound z-2 can be produced by reacting with compound z-1 in a solvent in the presence of a base or acid, and, if necessary, in the presence of a phase transfer catalyst.

Kind of base: inorganic bases such as sodium hydroxide, potassium hydroxide, and lithium hydroxide; etc.

Amount of base: 0.9 to 10 moles relative to 1 mole of compound z-1

Kind of acid: hydrochloric acid, sulfuric acid, etc.

Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-1

Kind of phase transfer catalyst: tetrabutylammonium bromide etc.

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound z-3 from Compound z-2

Compound z-3 can be produced by heating compound z-2 in a solvent, if necessary, in the presence of an acid or base.

Kind of base: nitrogen-containing compounds such as quinoline and pyridine; amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; and mixtures thereof; etc.

Amount of base: 0.9 mole to an excess amount relative to 1 mole of compound z-2

Kind of acid: hydrochloric acid, sulfuric acid, etc.

Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-2

Kind of phase transfer catalyst: tetrabutylammonium bromide etc.

Solvent: amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; and mixtures thereof; etc.

Reaction temperature: 50° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

In this process, metal catalysts such as copper may be used in their catalytic amounts.

3) Process of Producing Compound z-24 from Compound z-23

Compound z-24 can be produced by reducing compound z-23 with iron powder in a solvent.

Amount of iron powder: 2 to 10 moles relative to 1 mole of compound z-23

Solvent: acetic acid, water, and mixtures thereof, etc.

Reaction temperature: 15° C. to 110° C.

Reaction time: a moment to 100 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound z-25 from Compound z-24

Compound z-25 can be produced by converting compound z-24 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with copper halide such as copper (I) chloride or copper (I) bromide.

(Diazonium salt formation)

Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-24

Kind of acid: sulfuric acid, hydrochloric acid, etc.

Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-24

Solvent: water, ethanol, hydrochloric acid, etc.

Reaction temperature: −15° C. to room temperature

Reaction time: a moment to 24 hours

(Reaction with copper halide)

Kind of copper halide: copper (C) chloride, copper (I) bromide, etc.

Amount of copper halide: 1 to 10 moles relative to 1 mole of compound z-24

Solvent: hydrochloric acid, hydrobromic acid, etc.

Reaction temperature: −10° C. to 80° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

5) Process of Producing Compound z-3 from Compound z-24

Compound z-3 can be produced by converting compound z-24 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt in a solvent.

(Diazonium salt formation)

Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-24

Kind of acid: sulfuric acid, hydrochloric acid, etc.

Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-24

Solvent: water, ethanol, hydrochloric acid, etc.

Reaction temperature: −15° C. to room temperature

Reaction time: a moment to 24 hours

(Thermal decomposition).

Solvent: sulfuric acid, water, etc.

Reaction temperature: room temperature to 200° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 25

This is the producing process according to the following scheme:

wherein R¹, R³, R⁴, R¹¹, Q, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, by the following processes.

1) Process of Producing Compound z-5 from Compound z-4

Compound z-5 can be produced by demethylating compound z-4 in a solvent in the presence of an acid or trimethylsilane iodide.

Kind of acid: inorganic acids such as hydrochloric acid and sulfuric acid; Lewis acids such as boron tribromide and aluminum chloride; etc.

Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-4

Amount of trimethylsilane iodide: 1 mole to an excess amount relative to 1 mole of compound z-4

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 168 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound z-6 from Compound z-5

Compound z-6 can be produced by reacting compound z-5 with compound z-18 of the general formula:

M⁹—R¹¹  z-18

wherein M⁹ and R¹¹ are as defined above, in a solvent in the presence of a base.

Amount of compound z-18: 1 to 2 moles relative to 1 mole of compound z-5

Kind of base: potassium carbonate, sodium hydride, etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound z-5

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: −10° C. to 100° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 26

This is the producing process according to the following scheme:

wherein R¹, R⁴, Q, T, A, and Y are as defined above; R²²² is —OR¹¹ or —SR¹² wherein R¹¹ and R¹² are as defined above; and R²²³ is —OR²²⁴ or —SR²²⁵ wherein R²²⁴ and R²²⁵ are the same or different and independently hydrogen, C₁-C₁₀ alkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl; C₃-C₁₀ alkynyl, C₁-C₅ alkoxy C₁-C₅ allkyl, C₁-C₅ alkylthio C₁-C₅ alkyl, or optionally substituted phenyl.

The reactions in the respective steps can be carried out, for example, by the following processes.

1) Process of Producing Compound z-8 from Compound z-7

Compound z-8 can be produced by reacting compound z-19 of the general formula:

H—R²²²  z-19

wherein R²²² is as defined above, in a solvent in the presence of a base.

Amount of compound z-19: 1 to 5 moles relative to 1 mole of compound z-7

Kind of base: organic bases such as triethylamine, inorganic bases such as potassium carbonate and sodium hydride; alkoxides such as sodium methoxide and sodium thiomethoxide; etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound z-7

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof, etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours;

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound z-8 wherein R²²² is —OR²²⁴ or —SR²²⁵; and R²²⁴ and R²²⁴ are as defined above (hereinafter referred to as compound z-8′) can be used to produce compound z-9 or compound z-10 as shown in the following processes.

2) Process of Producing Compound z-9 from Compound z-8′

Compound z-9 can be produced by reducing compound z-8′ with iron powder in a solvent.

Amount of iron powder: 2 to 10 moles relative to 1 mole of compound z-8′

Solvent: acetic acid, water, and mixtures thereof; etc.

Reaction temperature: 15° C. to 110° C.

Reaction time: a moment to 100 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound z-10 from Compound z-9

Compound z-10 can be produced by converting compound z-9 into a diazonium salt with sodium nitrite in the presence of an acid and then reacting the diazonium salt with a chloride such as copper (I) chloride.

(Diazonium salt formation)

Amount of sodium nitrite: 1 to 2 moles relative to 1 mole of compound z-9

Kind of acid: hydrochloric acid, etc.

Amount of acid: 1 mole to 100 moles relative to 1 mole of compound z-9

Solvent: water, ethanol, hydrochloric acid, etc.

Reaction temperature: −15° C. to room temperature

Reaction time: a moment to 24 hours

(Reaction with chloride)

Kind of chloride: copper (a) chloride etc.

Amount of chloride: 1 to 10 moles relative to 1 mole of compound z-9

Solvent: hydrochloric acid etc.

Reaction temperature: −10° C. to 80° C.

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

PRODUCING PROCESS 27

This is the producing process according to the following process:

wherein R¹, R³, R⁴, R¹⁴, R¹⁷, R¹⁹, Q, T, A, and Y are as defined above.

The reactions in the respective steps can be carried out, for example, by the following processes.

1) Process of Producing Compound z-12 from Compound z-11

Compound z-12 can be produced by reacting compound z-11 with copper (I) cyanide in a solvent.

Amount of copper (I) cyanide: 1 to 4 moles relative to 1 mole of compound z-11

Kind of solvent: amides such as N,N-dimethylformamide and N-methylpyrrolidone; sulfur compound such as dimethylsulfoxide; etc.

Reaction temperature: 40° C. to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound z-13 from Compound z-12

Compound z-13 can be produced by reacting compound z-12 with water in the presence of an acid.

Amount of water: 1 mole to an excess amount relative to 1 mole of compound z-12

Kind of acid: hydrochloric acid, sulfuric acid, etc.

Amount of acid: 1 mole to an excess amount relative to 1 mole of compound z-12

Reaction temperature: 10° C. to 50° C.

Reaction time: a moment to 24 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound z-14 from Compound z-13

Compound z-14 can be produced by reacting compound z-13 with water in the presence of an acid or base.

Amount of water: 1 equivalent to an excess amount relative to 1 mole of compound z-13

Kind of acid: hydrochloric acid, sulfuric acid, etc.

Amount of acid: 1 equivalent to an excess amount relative to 1 mole of compound z-13

Kind of base: sodium hydroxide, potassium hydroxide, etc.

Amount of base: 1 to 3 equivalents relative to 1 mole of compound z-13

Reaction temperature: room temperature to 150° C.

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound z-17 from Compound z-14

Compound z-17 can be produced by reacting compound z-14 with thionyl chloride to form an acid chloride compound (reaction 1) and then reacting the acid chloride compound with compound z-20 of the general formula:

HO—R¹⁴  z-20

wherein R¹⁴ is as defined above, in a solvent in the presence of a base (reaction 2).

(Reaction 1)

Amount of thionyl chloride: 1 mole to an excess amount relative to compound z-14

Reaction temperature: 40° C. to the reflux temperature of thionyl chloride

Reaction time: a moment to 10 hours

After completion of the reaction, the reaction mixture was concentrated and used as the starting material for reaction 2.

(Reaction 2)

Amount of compound z-20: 1 mole to an excess amount relative to 1 mole of compound z-14

Kind of base: pyridine, triethylamine, potassium carbonate, etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound z-14

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

5) Process of Producing Compound z-17 from Compound z-13

Compound z-17 can be produced by reacting compound z-13 with compound z-20 of the general formula:

HO—R¹⁴  z-20

wherein R¹⁴ is as defined above, in a solvent in the presence of a boron trihalide compound.

Amount of compound z-20: 1 mole to an excess amount relative to 1 mole of compound z-13

Kind of boron trihaihde compound: boron trifluoride, boron trichloride, boron tribromide, etc.

Amount of boron trihalide compound: 1 mole to an excess amount relative to 1 mole of compound z-13

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 50° C. to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

6) Process of Producing Compound z-15 from Compound z-12

Compound z-15 can be produced by reacting compound z-12 with compound z-2 1 of the general formula:

M¹¹—Mg—R¹⁷  z-21

wherein R¹⁷ is as defined above and M¹¹ is chlorine or bromine, in a solvent.

Amount of compound z-21: 1 to 1.3 moles relative to 1 mole of compound z-12

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; halogenated hydrocarbons such as chloroform; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

7) Process of Producing Compound z-16 from Compound z-15

Compound z-16 can be produced by reacting compound z-15 with compound z-22 of the general formula:

R¹⁹ONH₂  z-22

wherein R¹⁹ is as defined above, in a solvent, if necessary, in the presence of a base.

Amount of compound z-22: 1 to 3 moles relative to 1 mole of compound z-15

Kind of base: triethylamine, pyridine, potassium carbonate, etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound z-15

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

In addition to the above processes, the present compounds can also be produced by making reference to, for example, JP-A 5-213970, EP 683160-A1, and JP-A 61-161288.

The processes of producing some of the starting materials used in the production of the present compounds are explained below.

REFERENCE PRODUCING PROCESS 1

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, and Y¹¹ are as defined above; and R²⁵⁰ is carboxy, methoxycarbonyl, ethoxycarbonyl, aminocarbonyl, or nitrile.

The reactions in the respective steps can be carried out, for example, according to the processes as described in Indian Journal of Chemistry. (vol. 20B, pp. 391-393, 1981), Indian Journal of Chemistry (vol. 14B, pp. 6886-6891, 1981), Organic Syntheses (vol. 33, p. 43, 1953), or for example, by the following processes.

1) Process of Producing Compound v-2 from Compound v-1

Compound v-2 can be produced by reacting compound v-1 with compound v-19 of the general formula:

wherein R²⁵⁰ is as defined above and M²⁰ is chlorine, bromine, or iodine, in a solvent in the presence of a base.

Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound v-1

Amount of compound v-19: 0.9 to 3 moles relative to 1 mole of compound v-1

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof, etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound v-3 from Compound v-2

Compound v-3 can be produced by reacting compound v-2 in a solvent in the presence of a base.

Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 1 to 10 moles relative to 1 mole of compound v-2

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound v-4 from Compound v-3

Compound v-4 can be produced by reacting compound v-3 in a solvent in the presence of a base or acid and, if necessary, in the presence of a phase transfer catalyst.

Kind of base: inorganic bases such as sodium hydroxide and potassium hydroxide; etc.

Amount of base: 0.9 to 10 moles relative to 1 mole of compound v-3

Kind of acid: hydrochloric acid, sulfuric acid, etc.

Amount of acid: 1 mole to an excess amount relative to 1 mole of compound v-3

Kind of phase transfer catalyst: tetrabutylammonium bromide etc.

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; water; and mixtures thereof; etc.

Reaction temperature: 10° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

4) Process of Producing Compound v-5 from Compound v-4

Compound v-5 can be produced by heating compound v-4 in a solvent, if necessary, in the presence of a base or acid.

Kind of base: nitrogen-containing compounds such as quinoline and pyridine; amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; and mixtures thereof; etc.

Amount of base: 0.9 mole to an excess amount relative to 1 mole of compound v-4

Kind of acid: hydrochloric acid, sulfuric acid, etc.

Amount of acid: 1 mole to an excess amount relative to 1 mole of compound v-4

Solvent: amides such as N,N-dimethylformamide; sulfur compounds such as sulforane; aromatic hydrocarbons such as xylene and mesitylene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran and 1,4-dioxane; and mixtures thereof, etc.

Reaction temperature: 50° C. to the reflux temperature of the solvent

Reaction time: a moment to 96 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

In this process, metal catalysts such as copper may be used.

Compound v-1 as the starting material in this producing process can also be produced from the corresponding benzaldehyde derivative by making reference to, for example, Shin Jikken Kagaku Koza (published by Maruzen Kabushiki Kaisha) vol. 14, pp. 1466-1470. The benzaldehyde derivative to be used as the starting material at that time can also be produced by making reference to, for example, EP 0312338-A1, Synthetic Communication, 24(12), pp. 1757-1760 (1994), and J. Chem. Soc. Perkin I, pp. 318-321 (1978).

Compound v-2 as the intermediate can also be produced according to the following scheme 1 or 2.

wherein R¹, R², R³, R⁴, R²⁵⁰, and Y¹¹ are as defined above; and M²¹ is fluorine, chlorine, or bromine.

5) Process of Producing Compound v-2 from Compound v-6

Compound v-2 can be produced by reacting compound v-6 with compound v-17 of the formula:

wherein Y¹¹ and R²⁵⁰ are as defined above, in a solvent in the presence of a base.

Kind of base: inorganic bases such as potassium carbonate, sodium hydride, sodium hydroxide, and potassium fluoride; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; etc.

Amount of base: 1 to 10 moles relative to 1 mole of compound v-6

Amount of compound v-17: 0.9 to 10 moles relative to 1 mole of compound v-6

Solvent: aromatic hydrocarbons such as benzene and toluene; halo-genated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran and 1,4-dioxane; amides such as N,N-dimethylformamide; and mixtures thereof; etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 72 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

wherein R¹, R², R³, R⁴, R²⁵⁰, and Y¹¹ are as defined above.

1) Process of Producing Compound v-2 from Compound v-16

Compound v-2 can be produced by reacting compound v-16 with copper (I) cyanide in a solvent.

Amount of copper (I) cyanide: 1 to 4 moles relative to 1 mole of compound v-16

Kind of solvent: amides such as N,N-dimethylformamide and N-methylpyrrolidone; sulfur compound such as dimethylsulfoxide; etc.

Reaction temperature: 40° C. to the reflux temperature of the solvent

Reaction time: a moment to 120 hours

After completion of the reaction, ammonia water is added, if necessary, to the reaction mixture, which is then extracted with an organic solvent, and the organic layer is dried and concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

REFERENCE PRODUCING PROCESS 2

This is the producing process according to the following scheme:

wherein R¹, ², R³, and R⁴ are as defined above; and M²² is fluorine or chlorine.

The reactions in the respective steps can be carried out, for example, according to the processes as described in Tetrahedron Letters (vol. 37, No. 17, pp. 2885-2886, 1996), or for example, by the following processes.

1) Process of Producing Compound v-8 from Compound v-7

Compound v-8 can be produced by reacting compound v-7 with aceto-hydroxamic acid in a solvent in the presence of a base.

Amount of hydroxamic acid: 1 to 3 moles relative to 1 mole of compound v-7

Kind of base: potassium t-butoxide, sodium hydride, etc.

Amount of base: 1 to 3 moles relative to 1 mole of compound v-7

Solvent: N,N-dimethylformamide, dimethylsulfoxide, tetrahydrofuran, etc.

Reaction temperature: room temperature to 100° C.

Reaction time a moment to 100 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

REFERENCE PRODUCING PROCESS 3

This is the producing process according to the following scheme:

wherein R¹, R², R³, and R⁴ are as defined above; Y¹ is oxygen, sulfur, or N-R¹⁴²; and R¹⁴² is as defined above.

The reactions in the respective steps can be carried out, for example, by the following processes.

1) Process of Producing Compound v-10 from Compound v-9

Compound v-10 can be produced by reacting compound v-9 with a nitrating agent in a solvent or without solvent.

Kind of nitrating agent: nitric acid etc.

Amount of nitrating agent: 1 to 1.5 moles relative to 1 mole of compound v-9

Solvent: acetic anhydride etc.

Reaction temperature: −10° C. to 50° C.

Reaction time: a moment to 100 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound v-11 from Compound v-10

Compound v-11 can be produced by reducing compound v-10 with iron powder in a solvent.

Amount of iron powder: 1 to 10 moles relative to 1 mole of compound v-10

Solvent: acetic acid, water, and mixtures thereof, etc.

Reaction temperature: 15° C. to 110° C.

Reaction time: a moment to 100 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

REFERENCE PRODUCING PROCESS 4

This is the producing process according to the following scheme:

wherein R²²⁶ is C₁-C₁₀ alkyl and M¹² is fluorine or chlorine.

The reactions in the respective steps can be carried out, for example, according to the processes as described in Khim. Geterotsikl. Soedin (1990, Issue 5, pp. 597-600), Khim. Geterotsikl. Soedin (1989, Issue 5, pp. 704), or for example, by the following processes.

1) Process of Producing Compound v-13 from Compound v-12

Compound v-13 can be produced by reacting compound v-12 with nitroenamine compound v-18 of the formula:

in a solvent and, if necessary, in the presence of an acid.

Amount of compound v-18: 1 to 3.0 moles relative to 1 mole of compound v-12

Kind of acid: acetic acid, p-toluenesulfonic acid, sulfuric acid, etc.

Amount of acid: a catalytic amount to a large excess amount relative to 1 mole of compound v-12

Solvent: aromatic hydrocarbons such as toluene and xylene; ethers such as tetrahydrofuran; organic acids such as acetic acid and propionic acid; amides such as N,N-dimethylformamide; and mixtures thereof; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 100 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

2) Process of Producing Compound v-14 from Compound v-13

Compound v-14 can be produced by reacting compound v-13 with an alkylcarbonylating agent in a solvent and, if necessary, in the presence of an acid and a base.

Kind of alkylcarbonylating agent: acetic anhydride, acetyl chloride, etc.

Amount of alkylcarbonylating agent: 1 to 2.0 moles relative to 1 mole of compound v-13

Kind of acid: acetic acid, p-toluenesulfonic acid, sulfuric acid, etc.

Amount of acid: a catalytic amount to a large excess amount relative to 1 mole of compound v-13

Kind of base: sodium hydroxide, potassium carbonate, triethylamine, etc.

Amount of base: a catalytic amount to a large excess amount relative to 1 mole of compound v-13

Solvent: aromatic hydrocarbons such as toluene and xylene; ethers such as tetrahydrofuran; organic acids such as acetic acid and propionic add; inorganic acids such as sulfuric acid; amides such as N,N-dimethylformamide; and mixtures thereof; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 100 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

3) Process of Producing Compound v-15 from Compound v-14

Compound v-15 can be produced by reducing compound v-14 with iron powder in a solvent.

Amount of iron powder: 1 to 10 moles relative to 1 mole of compound v-14

Solvent: acetic acid, water, and mixtures thereof, etc.

Reaction temperature: 15° C. to 110° C.

Reaction time: a moment to 100 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

REFERENCE PRODUCING PROCESS 5

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, and A are as defined above; Y² is nitrogen or C—R¹⁵²; and R¹⁵² is as defined above.

The reaction can be carried out, for example, according to the processes as described in Synthesis (Issue 1, pp. 1-17, 1977), J. Med. Chem. (Vol. 39, pp. 570-581, 1996), or for example, by the following process.

1) Process of Producing Compound x-3 from Compound x-5

Compound x-3 can be produced by reacting compound x-5 with an aminating agent in a solvent in the presence of a base.

Kind of base: inorganic bases such as potassium carbonate, sodium hydride, sodium hydroxide, and potassium hydroxide; etc.

Amount of base: 1 to 20 moles relative to 1 mole to compound x-5

Kind of aminating agent: hydroxylamine=O-sulfonic acid, chloramine, O-(2,4-dinitrophenyl)hydroxylamine, etc.

Amount of aminating agent: 0.9 to 5 moles relative to 1 mole of compound x-5

Solvent: aromatic hydrocarbons such as benzene and toluene; halogenated aromatic hydrocarbons such as chlorobenzene; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof; etc.

Reaction temperature: −10° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

Compound x-5 used as the intermediate in the above reaction can be produced, for example, according to the processes as described in JP-A 7-508259, JP-A 7-508500, WO93/18008, and WO94/25446.

REFERENCE PRODUCING PROCESS 6

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, and Y¹¹ are as defined above.

The reaction can be carried out, for example, according to the process as described in Chem. Pharm. Bull. 32(11), pp. 4260-4270 (1984), or for example, by the following scheme:

1) Process of Producing Compound v-20 from Compound v-1

Compound v-20 can be produced by reacting compound v-1 with bromonitromethane in a solvent in the presence of a base.

Kind of base: inorganic bases such as potassium carbonate, sodium hydride, and sodium hydroxide; organic bases such as triethylamine; nitrogen-containing compounds such as pyridine; metal alcoholates such as sodium methylate and sodium ethylate; etc.

Amount of base: 1 to 5 moles relative to 1 mole of compound v-1

Amount of bromonitromethane: 0.9 to 3 moles realtive to 1 mole of compound v-1

Solvent: aromatic hydrocarbons such as benzene and toluene;

halogenated aromatic hydrocarbons such as chlorobenzene; ketones such as acetone; ethers such as tetrahydrofuran; amides such as N,N-dimethylformamide; alcohols such as methanol, ethanol, and isopropanol; and mixtures thereof, etc.

Reaction temperature: 0° C. to the reflux temperature of the solvent

Reaction time: a moment to 48 hours

After completion of the reaction, the reaction mixture is subjected to post-treatments, for example, the reaction mixture is poured into water, and the deposited crystals are collected by filtration and dried; or the reaction mixture is extracted with an organic solvent, and the organic layer was dried and concentrated; or the reaction mixture is concentrated, thereby obtaining the desired compound. The compound can be purified by a technique such as recrystallization or column chromatography.

REFERENCE PRODUCING PROCESS 7

This is the producing process according to the following scheme:

wherein R¹, R², R³, R⁴, R²²¹, Y¹¹, and Q are as defined above.

The reactions in the respective steps can be carried out according to the processes as described in Producing Processes 1 to 23.

The benzonitrile derivatives used in Reference Producing Processes 1 and 2 can be produced from the corresponding benzaldehyde derivatives or benzamide derivatives. (see Shin Jikken Kagaku Koza, edited by Nihon Kagaku Kai, Maruzen Kabushiki Kaisha, 14, pp. 1466-1474)

Examples of the present compounds which can be prepared according to the above producing process are illustrated below; however, the present invention is not limited to these examples.

In the examples, Me indicates methyl; Et, ethyl; Pr, propyl; Bu, butyl; Pen, pentyl; Hex, hexyl; Hep, heptyl; Oct, octyl; i-, iso-; s-, sec-; c-, cyclo-; and groups not particularly indicated are in normal form.

Compounds of the general formulas:

wherein

A's are selected from nitrogen or CH;

Y¹'s are selected from oxygen or sulfur;

Y²'s are selected from nitrogen or CH,

R²'s are selected from hydrogen, fluorine, chlorine, bromine, iodine, CH₂OH, CHO, COOH, CONH₂, COCl, SO₂Cl, COGH₃; SH, OH, NH₂, NO₂, CN, CH₃, CH₂Br, CHB₂, CBr₃, CH₂F, CHF₂, CF₃, O-Me, O-Et, O-Pr, O-i-Pr, O-Bu, O-i-Bu, O-s-Bu, O-Pen, O-c-Pen, O-Hex, O-c-Hex, O-Hep, O-Oct, OCH₂CH₂F, OCH₂CH₂Cl, OCH₂CH₂Br, OCH₂CF₃, OCH₂OCH₃, OCH₂CH₂OCH₃, OCH₂CH₂OCH₂CH₃, OCH₂SCH₃, OCH₂CH₂SCH₃, OCH₂CH₂SCH₂CH₃, OCH₂CH═CH₂, OCH(CH₃)CH═CH₂, OC(CH₃)₂CH═CH₂, OCH₂C(Cl)═CH₂, OCH(CH₃)C(Cl)═CH₂, OCH₂C(CH₃)═CH₂, OCH₂C≡CH, OCH(CH₃)C≡CH, OC(CH₃)₂C≡CH, OCH₂-c-Pr, OCH₂-c-Pen, OCH₂-c-Hex, OCH₂CN, OCH(CH₃)CN, OCOMe, OCOEt, OCOPr, OCO-i-Pr, OCOCF₃, OCOCF₂H, OCH₂COOH, OCH₂COOMe, OCH₂COOEt, OCH₂GOOPr, OCH₂COO-i-Pr, OCH₂COOBu, OCH₂COO-s-Bu, OCH₂COOPen, OCH₂COOHex, OCH₂COOHep, OCH₂COO-c-Pen, OCH₂COO-c-Hex, OCH₂COOCH₂CH═CH₂, OCH₂COOCH₂C≡OCH, OCH₂COOPh, OCH₂COOCH₂Ph, OCH₂C(═NOMe)COOMe, OCH₂C(═NOMe)COOEt, OCH₂C(═NOMe)COOPr, OCH₂COOCH₂COOH, OCH₂COOCH₂COOMe, OCH₂COOCH₂COOEt, OCH₂COOCH₂COOPr, OCH₂COOCH₂COO-i-Pr, OCH₂COOCH₂COOBu, OCH₂COOCH₂COO-c-Pen, OCH₂COOCH₂COO-c-Hex, OCH₂COOCH₂COOCH₂CH═CH₂, OCH₂COOCH₂COOCH₂C≡CH, OCH₂COOCH(CH₃)COOH, OCH₂COOCH(CH₃)COOMe, OCH₂COOCH(CH₃)COOEt, OCH₂COOCH(CH₃)COOPr, OCH₂COOCH(CH₃)COO-i-Pr, OCH₂COOCH(CH₃)COOBu, OCH₂COOCH(CH₃)COO-c-Pen, OCH₂COOCH(CH₃)COO-c-Hex, OCH₂COOCH(CH₃)COOCH₂CH═CH₂, OCH₂COOCH(CH₃)COOCH₂C≡CH, OCH₂COOC(CH₃)₂COOH, OCH₂COOC(CH₃)₂COOMe, OCH₂COOC(CH₃)₂COOEt, OCH₂COOC(CH₃)₂COOPr, OCH₂COOC(CH₃)₂COO-i-Pr, OCH₂COOC(CH₃)₂COOBu, OOH₂COOC(CH₃)₂COO-c-Pen, OCH₂COOC(CH₃)₂COO-c-Hex, OCH₂COOC(CH₃)₂COOCH₂CH═CH₂, OCH₂COOC(CH₃)₂COOCH₂C≡CH, OCH(CH₃)COOH, OCH(CH₃)COOMe, OCH(CH₃)COOEt, OCH(CH₃)COOPr, OCH(CH₃)COO-i-Pr, OCH(CH₃)COOBu, OCH(CH₃)COO-s-Bu, OCH(CH₃)COOPen, OCH(CH₃)COOHex, OCH(CH₃)COOHep, OCH(CH₃)COO-c-Pen, OCH(CH₃)COO-c-Hex, OCH(CH₃)COOCH₂CH═CH₂, OCH(CH₃)COOCH₂C≡CH, OCH(CH₃)COOPh, OCH(CH₃)COOCH₂Ph, OCH(CH₃)C(═NOMe)COOMe, OCH(CH₃)C(═NOMe)COOEt, OCH(CH₃)C(═NOMe)COOPr, OCH(CH₃)COOCH₂COOH, OCH(CH₃)COOCH₂COOMe, OCH(CH₃)COOCH₂COOEt, OCH(CH₃)COOCH₂COOPr, OCH(CH₃)COOCH₂COO-i-Pr, OCH(CH₃)COOCH₂COOBu, OCH(CH₃)COOCH₂COO-c-Pen, OCH(CH₃)COOCH₂COO-c-Hex, OCH(CH₃)COOCH₂COOCH₂CH═CH₂, OCH(CH₃)COOH₂COOCH₂C≡CH, OCH(CH₃)COOCH(CH₃)COOH, OCH(CH₃)COOH(CH₃)COOMe, OCH(CH₃)COOCH(CH₃)COOEt, OCH(CH₃)COOCH(CH₃)COOPr, OCH(CH₃)COOCH(CH₃)COO-i-Pr, OCH(CH₃)COOCH(CH₃)COOBu, OCH(CH₃)COOCH(CH₃)COO-c-Pen, OCH(CH₃)COOCH(CH₃)COO-c-Hex, OCH(CH₃)COOCH(CH₃)COOCH₂CH═CH₂, OCH(CH₃)COOCH(CH₃)COOCH₂C≡CH, OCH(CH₃)COOC(CH₃)₂COOH, OCH(CH₃)COOC(CH₃)₂COOMe, OCH(CH₃)COOC(CH₃)₂COOEt, OCH(CH₃)COOC(CH₃)₂COOPr, OCH(CH₃)COOC(CH₃)₂COO-i-Pr, OCH(CH₃)COOC(CH₃)₂COOBu, OCH(CH₃)COOC(CH₃)₂COO-c-Pen, OCH(CH₃)COOC(CH₃)₂COO-c-Hex, OCH(CH₃)COOC(CH₃)₂COOCH₂CH═CH₂, OCH(CH₃)COOC(CH₃)₂COOCH₂C≡CH, OCH₂CON(Me)₂, OCH₂CON(Et)₂, OCH(CH₃)CON(Me)₂, OCH(CH₃)CON(Et)₂, S-Me, S-Et, S-Pr, S-i-Pr, S-Bu, S-i-Bu, S-s-Bu, S-Pen, S-c-Pen, S-Hex, S-c-Hex, S-Hep, S-Oct, SCH₂CH₂F, SCH₂CH₂Cl, SCH₂CH₂Br, SCH₂CF₃, SCH₂OCH₃, SCH₂CH₂OCH₃, SCH₂CH₂OCH₂CH₃, SCH₂SCH₃, SCH₂CH₂SCH₃, SCH₂CH₂SCH₂CH₃, SCH₂CH═CH₂, SCH(CH₃)CH═CH₂, SC(CH₃)₂CH═CH₂, SCH₂C(Cl)CH₂, SCH(CH₃)C(Cl)═CH₂, SCH₂C(CH₃)═CH₂, SCH₂C≡CH, SCH(CH₃)C≡CH, SC(CH₃)₂C≡CH, SCH₂-c-Pr, SCH₂-c-Pen, SCH₂-c-Hex, SCH₂CN, SCH(CH₃)CN, SCOMe, SCOEt, SCOPr, SCO-i-Pr, SCOCF₃, SCOCF₂H, SCH₂COOH, SCH₂COOMe, SCH₂COOEt, SCH₂COOPr, SCH₂COO-i-Pr, SCH₂COOBu, SCH₂COO-s-Bu, SCH₂COOPen, SCH₂COOHex, SCH₂COOHep, SCH₂COO-c-Pen, SCH₂COO-c-Hex, SCH₂COOCH₂CH═CH₂, SCH₂COOCH₂C≡CH, SCH₂COOPh, SCH₂COOCH₂Ph, SCH₂COOCH₂COOH, SCH₂COOCH₂COOMe, SCH₂COOCH₂COOEt, SCH₂COOCH₂COOPr, SCH₂COOCH₂COO-i-Pr, SCH₂COOCH₂COOBu, SCH₂COOCH₂COO-c-Pen, SCH₂COOCH₂COO-c-Hex, SCH₂COOCH₂COOCH₂CH═CH₂, SCH₂COOCH₂COOCH₂C≡CH, SCH₂COOCH(CH₃)COOH, SCH₂COOCH(CH₃)COOMe, SCH₂COOCH(CHOCOOEt, SCH₂COOCH(CH₃)COOPr, SCH₂COOCH(CH₃)COO-i-Pr, SCH₂COOCH(CH₃)COOBu, SCH₂COOCH(CH₃)COO-c-Pen, SCH₂COOH(CH₃)COO-c-Hex, SCH₂COOCH(CH₃)COOCH₂CH═CH₂, SCH₂COOH(CH₃)COOCH₂C≡CH, SCH₂COOC(CH₃)₂COOH, SCH₂COOC(CH₃)₂COOMe, SCH₂COOC(CH₃)₂COOEt, SCH₂COOC(CH₃)₂COOPr, SCH₂COOC(CH₃)₂COO-i-Pr, SCH₂COOC(CH₃)₂COOBu, SCH₂COOC(CH₃)₂COO-c-Pen, SCH₂COOC(CH₃)₂COO-c-Hex, SCH₂COOC(CH₃)₂COOCH₂CH═CH₂, SCH₂COOC(CH₃)₂COOCH₂C≡CH, SCH(CH₃)COOH, SCH(CH₃)COOMe, SCH(CH₃)COOEt, SCH(CH₃)COOPr, SCH(CH₃)COO-i-Pr, SCH(CH₃)COOBu, SCH(CH₃)COO-s-Bu, SCH(CH₃)COOPen, SCH(CH₃)COOHex, SCH(CH₃)COOHep, SCH(CH₃)COO-c-Pen, SCH(CH₃)COO-c-Hex, SCH(CH₃)COOCH₂CH═CH₂, SCH(CH₃)COOCH₂C≡CH, SCH(CH₃)COOPh, SCH(CH₃)COOCH₂Ph, SCH(CH₃)COOCH₂COOH, SCH(CH₃)COOCH₂COOMe, SCH(CH₃)COOCH₂COOEt, SCH(CH₃)COOCH₂COOPr, SCH(CH₃)COOCH₂COO-i-Pr, SCH(CH₃)COOCH₂COOBu, SCH(CH₃)COOCH₂COO-c-Pen, SCH(CH₃)COOCH₂COO-c-Hex, SCH(CH₃)COOCH₂COOCH₂CH═CH₂, SCH(CH₃)COOCH₂COOCH₂C≡CH, SCH(CH₃)COOCH(CH₃)COOH, SCH(CH₃)COOCH(CH₃)COOMe, SCH(CH₃)COOCH(CH₃)COOEt, SCH(CH₃)COOCH(CH₃)COOPr, SCH(CH₃)COOCH(CH₃)COO-i-Pr, SCH(CH₃)COOCH(CH₃)COOBu, SCH(CH₃)COOCH(CH₃)COO-c-Pen, SCH(CH₃)COOCH(CH₃)COO-c-Hex, SCH(CH₃)COOCH(CH₃)COOCH₂CH═CH₂, SCH(CH₃)COOCH(CH₃)COOCH₂C≡CH, SCH(CH₃)COOC(CH₃)₂COOH, SCH(CH₃)COOC(CH₃)₂COOMe, SCH(CH₃)COOC(CH₃)₂COOEt, SCH(CH₃)COOC(CH₃)₂COOPr, SCH(CH₃)COOC(CH₃)₂COO-i-Pr, SCH(CH₃)COOC(CH₃)₂COOBu, SCH(CH₃)COOC(CH₃)₂COO-c-Pen, SCH(CH₃)COOC(CH₃)₂COO-c-Hex, SCH(CH₃)COOC(CH₃)₂COOCH₂CH═CH₂, SCH(CH₃)COOC(CH₃)₂COOCH₂C≡CH, SCH₂CON(Me)₂, SCH₂CON(Et)₂, SCH(CH₃)CON(Me)₂, SCH(CH₃)CON(Et)₂, NH-Me, NH-Et, NH-Pr, NH-i-Pr, NH-Bu, NH-i-Bu, NH-s-Bu, NH-Pen, NH-c-Pen, NH-Hex, NH-c-Hex, NH-Hep, NH-Oct, NHCH₂CH═CH₂, NHCH(CH₃)CH═CH₂, NHC(CH₃)₂CH═CH₂, NHCH₂C(Cl)═CH₂, NHCH(CH₃)C(Cl)═CH₂, NHCH₂C(CH₃)═CH₂, NHCH₂C≡CH, NHCH(CH₃)C≡CH, NHC(CH₃)₂C≡CH, NHCH₂-c-Pr, NHCH₂-c-Pen, NHCH₂-c-Hex, NHCH₂CN, NHCH(CH₃)CN, NHCOMe, NHCOEt, NHCOPr, NHCO-i-Pr, NHCOCF₃, NHCOCF₂H, NHCOOMe, NHCOOEt, NHCOOPr, NHCOO-i-Pr, NHSO₂Me, NHSO₂Et, NHSO₂Pr, NHSO₂-i-Pr, NHSO₂CH₂Cl, NHSO₂CF₃, NHCH₂COOH, NHCH₂COOMe, NHCH₂COOEt, NHCH₂COOPr, NHCH₂COO-i-Pr, NHCH₂COOBu, NHCH₂COO-s-Bu, NHCH₂COOPen, NHCH₂COOHex, NHCH₂COOHep, NHCH₂COO-c-Pen, NHCH₂COO-c-Hex, NHCH₂COOCH₂CH═CH₂, NHCH₂COOCH₂C≡CH, NHCH₂COOPh, NHCH₂COOCH₂Ph, NHCH₂COOCH₂COOH, NHCH₂COOCH₂COOMe, NHCH₂COOCH₂COOEt, NHCH₂COOCH₂COOPr, NHCH₂COOCH₂COO-i-Pr, NHCH₂COOCH₂COOBu, NHCH₂COOCH₂COO-c-Pen, NHCH₂COOCH₂COO-c-Hex, NHCH₂COOCH₂COOCH₂CH═CH₂, NHCH₂COOCH₂COOCH₂C≡CH, NHCH₂COOCH(CH₃)COOH, NHCH₂COOCH(CH₃)COOMe, NHCH₂COOCH(CH₃)COOEt, NHCH₂COOCH(CH₃)COOPr, NHCH₂COOCH(CH₃)COO-i-Pr, NHCH₂COOCH(CH₃)COOBu, NHCH₂COOCH(CH₃)COO-c-Pen, NHCH₂COOCH(CH₃)COO-c-Hex, NHCH₂COOCH(CH₃)COOCH₂CH═CH₂, NHCH₂COOCH(CH₃)COOCH₂C≡CH, NHCH₂COOC(CH₃)₂COOH, NHCH₂COOC(CH₃)₂COOMe, NHCH₂COOC(CH₃)₂COOEt, NHCH₂COOC(CH₃)₂COOPr, NHCH₂COOC(CH₃)₂COO-i-Pr, NHCH₂COOC(CH₃)₂COOBu, NHCH₂COOC(CH₃)₂COO-c-Pen, NHCH₂COOC(CH₃)₂COO-c-Hex, NHCH₂COOC(CH₃)₂COOCH₂CH═CH₂, NHCH₂COOC(CH₃)₂COOCH₂C≡CH, NHCH(CH₃)COOH, NHCH(CH₃)COOMe, NHCH(CH₃)COOEt, NHCH(CH₃)COOPr, NHCH(CH₃)COO-i-Pr, NHCH(CH₃)COOBu, NHCH(CH₃)COO-s-Bu, NHCH(CH₃)COOPen, NHCH(CH₃)COOHex, NHCH(CH₃)COOHep, NHCH(CH₃)COO-c-Pen, NHCH(CH₃)COO-c-Hex, NHCH(CH₃)COOCH₂CH═CH₂, NHCH(CH₃)COOCH₂C≡CH, NHCH(CH₃)COOPh, NHCH(CH₃)COOCH₂Ph, NHCH(CH₃)COOCH₂COOH, NHCH(CH₃)COOCH₂COOMe, NHCH(CH₃)COOCH₂COOEt, NHCH(CH₃)COOCH₂COOPr, NHCH(CH₃)COOCH₂COO-i-Pr, NHCH(CH₃)COOCH₂COOBu, NHCH(CH₃)COOCH₂COO-c-Pen, NHCH(CH₃)COOCH₂COO-c-Hex, NHCH(CH₃)COOCH₂COOCH₂CH═CH₂, NHCH(CH₃)COOCH₂COOCH₂C≡CH, NHCH(CH₃)COOCH(CH₃)COOH, NHCH(CH₃)COOCH(CH₃)COOMe, NHCH(CH₃)COOCH(CH₃)COOEt, NHCH(CH₃)COOCH(CH₃)COOPr, NHCH(CH₃)COOCH(CH₃)COO-i-Pr, NHCH(CH₃)COOCH(CH₃)COOBu, NHCH(CH₃)COOCH(CH₃)COO-c-Pen, NHCH(CH₃)COOCH(CH₃)COO-c-Hex, NHCH(CH₃)COOCH(CH₃)COOCH₂CH═CH₂, NHCH(CH₃)COOCH(CH₃)COOCH₂C≡CH, NHCH(CH₃)COOC(CH₃)₂COOH, NHCH(CH₃)COOC(CH₃)₂COOMe, NHCH(CH₃)COOC(CH₃)₂COOEt, NHCH(CH₃)COOC(CH₃)₂COOPr, NHCH(CH₃)COOC(CH₃)₂COO-i-Pr, NHCH(CH₃)COOC(CH₃)₂COOBu, NHCH(CH₃)COOC(CH₃)₂COO-c-Pen, NHCH(CH₃)COOC(CH₃)₂COO-c-Hex, NHCH(CH₃)COOC(CH₃)₂COOCH₂CH═CH₂, NHCH(CH₃)COOC(CH₃)₂COOCH₂C≡CH, NHCH₂CON(Me)₂, NHCH₂CON(Et)₂, NHCH(CH₃)CON(Me)₂, NHCH(CH₃)CON(Et)₂, COOH, COOMe, COOEt, COOPr, COO-i-Pr, COOBu, COO-s-Bu, COOPen, COOHex, COOCH₂Ph, COO-c-Pen, COO-c-Hex, COOCH₂COOH, COOCH₂COOMe, COOCH₂COOEt, COOCH₂COOPr, COOCH₂COO-i-Pr, COOCH₂COOBu, COOCH₂COO-c-Pen, COOCH₂COO-c-Hex, COOCH₂COOCH₂CH═CH₂, COOCH₂COOCH₂C≡CH, COOCH(CH₃)COOH, COOCH(CH₃)COOMe, COOCH(CH₃)COOEt, COOCH(CH₃)COOPr, COOCH(CH₃)COO-i-Pr, COOCH(CH₃)COOBu, COOCH(CH₃)COO-c-Pen, COOCH(CH₃)COO-c-Hex, COOCH(CH₃)COOCH₂CH═CH₂, COOCH(CH₃)COOCH₂C≡CH, COOC(CH₃)₂COOH, COOC(CH₃)₂COOMe, COOC(CH₃)₂COOEt, COOC(CH₃)₂COOPr, COOC(CH₃)₂COO-i-Pr, COOC(CH₃)₂COOBu, COOC(CH₃)₂COO-c-Pen, COOC(CH₃)₂COO-c-Hex, COOC(CH₃)₂COOCH₂CH═CH₂, COOC(CH₃)₂COOCH₂C≡CH, CON(Et)₂, CON(Me)₂, CON(Et)₂, CH₂CH₂COOH, CH₂CH₂COOMe, CH₂CH₂COOEt, CH₂CH₂COOPr, CH₂CH₂COO-i-Pr, CH₂CH₂COOBu, CH₂CH(Cl)COOH, CH₂CH(Cl)COOMe, CH₂CH(Cl)COOEt, CH₂CH(Cl)COOPr, CH₂CH(Cl)COO-i-Pr, CH₂CH(Cl)COOBu, CH═CHCOOH, CH═CHCOOMe, CH═CHCOOEt, CH═CHCOOPr, CH═CHCOO-i-Pr, CH═CHCOOBu, CH═C(Cl)COOH, CH═C(Cl)COOMe, CH═C(Cl)COOEt, CH═C(Cl)COOPr, CH═C(Cl)COO-i-Pr, CH═C(Cl)COOBu, C(Me)═CHCOOH, C(Me)═CHCOOMe, C(Me)═CHCOOEt, C(Me)═CHCOOPr, C(Me)═CHCOO-i-Pr, C(Me)═CHCOOBu, CH═C(Me)COOH, CH═C(Me)COOMe, CH═C(Me)COOEt, CH═C(Me)COOPr, CH═C(Me)COO-i-Pr, CH═C(Me)COOBu, CH═NOH, CH═NOMe, CH═NOEt, CH═NOPr, CH═NO-i-Pr, CH═NOBu, C(Me)═NOH, C(Me)═NOMe, C(Me)═NEt, C(Me)═NOPr, C(Me)═NO-i-Pr, C(Me)═NOBu, CH═NOCH₂COOMe, CH═NOCH₂COOEt, CH═NOCH₂COOPr, CH═NOCH₂COO-i-Pr, CH═NOCH₂COOBu, C(Me)═NOCH₂COOMe, C(Me)═NOCH₂COOEt, C(Me)═NOCH₂COOPr, C(Me)═NOCH₂COO-i-Pr, or (Me)═NOCH₂COOBu;

R³′s are selected from hydrogen, fluorine, chlorine, bromine, iodine, NO₂, CN, O-Me, O-Et, O-Pr, O-i-Pr, O-Bu, O-i-Bu, O-s-Bu, O-Pen, O-c-Pen, O-Hex, O-c-Hex, O-Hep, O-Oct, OCH₂COOMe, OCH₂COOEt, OCH₂COOPr, OCH₂COO-i-Pr, OCH₂COOBu, OCH₂COO-s-Bu, OCH₂COOPen, OCH₂COOHex, OCH₂COOHep, OCH₂C(═NOMe)COOMe, OCH₂C(═NOMe)COOEt, OCH₂C(═NOMe)COOPr, OCH(CH₃)COOMe, OCH(CH₃)COOEt, OCH(CH₃)COOPr, OCH(CH₃)COO-i-Pr, OCH(CH₃)COOBu, OCH(CH₃)COO-s-Bu, OCH(CH₃)COOPen, OCH(CH₃)COOHex, OCH(CH₃)COOHep, OCH(CH₃)C(═NOMe)COOMe, OCH(CH₃)C(═NOMe)COOEt, or OCH(CH₃)C(═NOMe)COOPr; and

R⁴′s are selected from hydrogen, fluorine, chlorine, bromine, iodine, NO₂, or CN.

EXAMPLES

The present invention will be further illustrated by the following Production Examples, Formulation Examples, and lest Examples; however, the present invention is not limited to these Examples. The numbers of the present compounds are those as shown in Tables 1 to 54.

Production Example 1

To a suspension of 60.0 g of potassium carbonate in 300 ml of acetone was added 25 g of compound 1a and then added 35.7 g of ethyl bromoacetate, and the mixture was heated and stirred at the reflux-temperature of acetone for 1 hour. The reaction mixture was then cooled to room temperature and filtered to remove insoluble matter. The filtrate was concentrated to give 45.8 g of compound 1b as a crude product.

To a solution of 45.8 g of this crude product of compound 1b in 300 ml of N,N-dimethylformamide was added 30.0 g of potassium carbonate, and the mixture was heated and stirred at a temperature of 100° C. to 110° C. for 5 hours. The reaction mixture was then cooled to room temperature and poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated to give 36.5 g of compound 1c as crystals.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.44 (3H, t, J=7.09 Hz), 4.44 (2H, q, J=7.07 Hz), 4.65-5.38 (2H, br), 7.21-7.27 (1H, m), 7.44-7.57 (3H, m).

To a solution of 10.2 g of compound 1c in 50 ml of tetrahydrofaran was added 6.5 g of ethyl chloroformate and 7.3 g of N,N-diethylaniline, and the mixture was heated and stirred at the reflux temperature of tetrahydrofuran for 3 hours. The reaction mixture was then cooled to room temperature and poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated to give 13.05 g of compound 1d.

m.p.: 90.6° C.

To a suspension of 2.4 g of sodium hydride in 50 ml of N,N-dimethylformamide was added 11.0 g of ethyl 4,4,4-trifluoro-3-aminochrotonate below 10° C., and the mixture was stirred for 30 minutes. The reaction mixture was then warmed to room temperature, to which a solution of 13.0 g of compound 1d in 20 ml of N,N-dimethylformamide was added, and the reaction mixture was then warmed to 100° C. to 110° C., at which temperature the mixture was kept and stirred for 2.5 hours. The reaction mixture was then cooled to room temperature, to which 10.0 g of methyl iodide was added, and the mixture was stirred at room temperature overnight. The reaction mixture was then poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=4:1) to give 4.56 g of compound 1e.

m.p.: 107.2° C.

First, 1.0 g of compound 1e was added to 5 ml of 85% sulfuric acid, and the mixture was warmed to 110° C., heated and stirred for 5 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 0.81 g of compound 1f.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 3.59-3.60 (3H, m), 6.41 (1H, s), 7.26-7.67 (4H, m).

First, 0.7 g of compound 1f and 0.05 g of copper powder were added to 3 ml of quinoline, and the mixture was warmed to 150° C., at which temperature the mixture was kept and stirred for 1 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate 5:1) to give 0.43 g of compound 1g (the present compound 1-1).

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 3.51 (3H, m), 6.34 (1H, s), 7.21-7.54 (4H, m), 7.81 (1H, s).

Production Example 2

To 200 ml of ethanol were added 25 g of compound 2a and 10.9 g of hydroxylamine hydrochloride, and the mixture was stirred at room temperature overnight. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 26.06 g of compound 2b.

To a solution of 26.0 g of compound 2b in 100 ml of chloroform was added 22.4 g of 1,1′-carbonyldiimidazole under ice cooling, and the mixture was stirred at room temperature for 30 minutes, then heated and stirred at the reflux temperature of chloroform for 1 hour. The reaction mixture was then concentrated, and diluted hydrochloric acid was added to the residue, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated to give 15.88 g of compound 2c.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 7.46 (1H, d, J=2.45 Hz), 7.57 (1H, d, J=2.45 Hz).

To a suspension of 16.5 g of potassium carbonate in 80 ml of acetone was added 15 g of compound 2c and then added 14.6 g of ethyl bromoacetate, and the mixture was heated and stirred at the reflux temperature of acetone for 4 hours. The reaction mixture was then cooled to room temperature and filtered to remove insoluble matter, and the filtrate was then concentrated to give compound 2d as a crude product.

To a solution of this crude product of compound 2d in 150 ml of N,N-dimethylformamide was added 50.0 g of potassium carbonate, and the mixture was heated and stirred at a temperature of 90° C. to 100° C. for 30 minutes. The reaction mixture was then cooled to room temperature and poured into water, and the deposited crystals were collected by filtration. The crystals were washed with water and dried to give 21.49 g of compound 2e.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.44 (3H, t, J=7.07 Hz), 4.45 (2H, q, J=7.07 Hz), 4.82-5.13 (2H, br), 7.44-7.45 (2H, m).

To 60 ml of toluene were added 4.0 g of compound 2e, 2.8 g of trichloromethyl chloroformate, and 1 g of activated carbon (powder), and the. mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was then filtered, and the filtrate was concentrated to give 13.0 g of compound 2f as a crude product.

In a suspension of 0.64 g of sodium hydride in 20 ml of N,N-dimethylformamide was added 3.0 g of ethyl 4,4,4-trifluoro-3-aminichrotonate below 10° C., and the mixture was stirred for 30 minutes. 1b the reaction mixture was added dropwise at −30° C. a solution of 13.0 g of this crude product of compound 2f in 30 ml of tetrahydrofuran. After completion of the dropwise addition, the reaction mixture was warmed to room temperature and stirred at room temperature for 2 hours. To the reaction mixture was then added 3.0 g of methyl iodide, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, then and concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=4:1) to give 4.51 g of compound 2g.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.33 (3H, t, J=7.06 Hz), 3.59 (3H, m), 4.39 (2H, q, J=6.93 Hz), 6.39 (1H, s), 7.36 (1H, d, J=2.65 Hz), 7.51 (1H, d, J=2.65 Hz).

First, 4.5 g of compound 2g was added to 20 ml of 85% sulfuric acid, and the mixture was heated to 100° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried to give 3.57 g of compound 2h.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 3.59-3.60 (3H, m), 6.40 (1H, s), 7.38 (1H, d, J=1.77 Hz), 7.54 (1H, d, J=1.77 Hz).

To 10 ml of quinoline were added 3.0 g of compound 2h and 0.07 g of copper powder, and the mixture was heated to 120° C. to 150° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 1.62 g of compound 2i (the present compound 1-2).

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 3.59-3.60 (3H, m), 6.40 (1H, s), 7.24 (1H, d, J=1.89), 7.37 (1H, d, J=1.89), 7.93 (1H, s).

Production Example 3

To a solution of 9.77 g of acetohydroxamic acid in 150 ml of N,N-dimethylformamide was added 14.6 g of potassium t-butoxide at room temperature, and the mixture was. stirred at room temperature for 30 minutes. To the reaction mixture was added 10.5 g of compound 3a at room temperature, and the mixture was left undisturbed at room temperature for 3 days. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with n-hexane to give 6.95 g of compound 3b.

To 2 ml of propionic acid were added 500 mg of compound 3b and 567 mg of 3,4,5,6-tetrahydrophthalic anhydride, and the mixture was heated and stirred at the reflux temperature of propionic acid for 24 hours. The reaction mixture was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=5:1) to give 200 mg of compound 3c (the present compound 2-4).

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.84-1.89 (4H, m), 2.48-2.52 (4H, m), 7.31-7.40 (1H, m), 7.55-7.75 (3H, m).

Production Example 4

To a solution of 10.4 g of ethyl thioglycolate in 20 ml of N,N-dimethylformamide were added 12.4 g of potassium carbonate and 20 ml of N,N-dimethylformamide, and the mixture was warmed to 40° C. To the reaction mixture was added 10.0 g of compound 4a, and the mixture was warmed to 85° C., at which temperature the mixture was kept and stirred for 2 hours. The reaction mixture was left undisturbed at room temperature overnight. To the reaction mixture were then added 33.7 g of potassium carbonate and 30 ml of N,N-dimethylformamide, and the mixture was heated and stirred at 100° C. to 110° C. for 4 hours. The reaction solution was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=4:1) to give 14.44 g of compound 4b.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.39 (3H, t, J=7.09 Hz), 4.36 (2H, q, J=7.11 Hz), 5.90 (2H, bs), 7.34-7.74 (4H, m).

To a solution of 4.0 g of compound 4b in 50 ml of toluene was added 3.58 g of trichloromethyl chloroformate, and the mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was concentrated to give compound 4c as a crude product.

To a suspension of 0.87 g of sodium hydride in 15 ml of N,N-dimethylformamide was added 4.0 g of ethyl 4,4,4-trifluoro-3-aminochrotonate below 10° C., and the mixture was stirred for 30 minutes. To the reaction was then added dropwise at −30° C. a solution of this crude product of compound 4c in the whole amount dissolved in 50 ml of tetrahydrofuran. After completion of the dropwise addition, the mixture was warmed to room temperature and left undisturbed overnight. To the reaction mixture was then added 3.85 g of methyl iodide, and the mixture was stirred at room temperature for 3 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=4:1) to give 2.36 g of compound 4b as crystals.

m.p.: 112.6° C.

To 15 ml of 85% sulfuric acid was added 2.3 g of compound 4d, and the mixture was warmed to 110° C., at which temperature the mixture was kept and stirred for 15 minutes. The reaction mixture was then poured into water, and the precipitated crystals were collected by filtration and dried to give 1.61 g of compound 4e.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 3.58 (3H, m), 6.42 (1H, s), 7.41-7.91 (4H, m).

To 12 ml of quinoline were added 1.5 g of compound 4e and 0.06 g of copper powder, and the mixture was warmed to 120° C. to 140° C., at which temperature the mixture was kept and stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=4:1) to give 1.07 g of compound 4f (the present compound 1-3).

m.p.: 156.8° C.

Production Example 5

According to the process as described above in Production Example 2, compound 5a (the present compound 1-6) was produced from 2-hydroxy-5-nitrobenzaldehyde.

m.p.: 231.9° C. (decomposition).

To a mixed solvent of 40 ml of acetic acid and 20 ml of water was added 4.5 g of iron powder, to which suspension 4.5 g of compound 5a was added, and the mixture was heated and stirred at the reflux temperature of the solvent for 20 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with saturated aqueous sodium bicarbonate solution, dried over anhydrous magnesium sulfate, and then concentrated to give 2.64 g of compound 5b (the present compound 1-7).

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.25-3.82 (2H, br), 3.58 (3H, m), 6.39 (1H, s), 6.55 (1H, d, J=2.30 Hz), 6.71 (1H, dd, J=8.76 Hz, 2.30 Hz), 7.32 (1H, d, J=8.76 Hz), 7.73 (1H, s).

To a solution of 0.8 g of compound 5b dissolved in 6 ml of pyridine was added 0.3 g of methanesulfonyl chloride at room temperature, and the mixture was stirred for 2 hours. The reaction mixture was poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, with aqueous hydrochloric acid solution, and then with water, dried over anhydrous magnesium sulfate, and then concentrated. The deposited crystals were washed with t-butyl methyl ether to give 0.55 g of compound 5c (the present compound 1-10).

m.p.: 105.3° C.

Production Example 6

To 6 ml of methyl iodide was added 0.6 g of compound 5b, and the mixture was heated and stirred at the reflux temperature of methyl iodide for 4 hours. The reaction mixture was concentrated, and the residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.14 g of compound 6a (the present compound 1-8) and 0.065 g of compound 6b (the present compound 1-9).

Compound 6a.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 2.82 (3H, s), 3.57-3.58 (3H, m), 6.37-6.67 (3H, m), 7.33 (1H, d, J=8.85 Hz), 7.71 (1H, s).

Compound 6b.

m.p.: 166.1° C. (decomposition).

Production Example 7

To 10 ml of acetonitrile were added 0.53 g of copper (II) chloride and 0.57 g of isobutyl nitrite, to which 3 ml of ethyl acrylate was added under ice cooling, and the mixture was stirred for 10 minutes. A solution of 1.0 g of compound 5b dissolved in 5 ml of acetonitrile was then added to the reaction mixture under ice cooling. The mixture obtained was stirred for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 0.64 g of compound 7a (the present compound 1-407).

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.18 (3H, t, J.=7.12 Hz), 3.18-3.48 (2H, m), 3.56-3.57 (3H, m), 4.10-4.20 (2H, m), 4.41 (1H, t, J=7.43 Hz), 6.39 (1H, s), 7.19-7.49 (3H, m), 7.82 (1H, s).

Production Example 8

According to the process as described above in Production Example 2, compound 8a (the present compound 1-5) was produced from 2-hydroxy-5-methoxybenzaldehyde.

m.p.: 135.0° C.

To a solution of 0.64 g of compound 8a dissolved in 4 ml of chloroform was added 0.5 g of iodotrimethylsilane, and the mixture was kept and stirred at 40° C. to 50° C. for 10.5 hours. The mixture was then left undisturbed at room temperature for a half day, to which 0.5 g of iodotrimethylsilane was further added, and the mixture was further kept and stirred at 40° C. to 50° C. for 10.5 hours. The reaction mixture was then poured into ice water, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.37 g of compound 8b (the present compound 1-78).

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 3.58-3.59 (3H, m), 5.09 (1H, bs) 6.39 (1H, s), 6.68 (1H, d, J=2.32 Hz), 6.82 (1H, dd, J=8.83 Hz, 2.32 Hz), 7.37 (1H, d, J=8.85 Hz), 7.79 (1H, s).

To a suspension of 0.05 g of sodium hydride in 1 ml of N,N-dimethylformamide was added a solution of 0.35 g of compound 8b in 2 ml of N,N-dimethylformamide under ice cooling, and the mixture was stirred for 5 minutes. Then, 0.23 g of ethyl bromoacetate was added under ice cooling, and the mixture was stirred for 0.5 hour. The reaction mixture was poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.34 g of compound 8c (the present compound 1-127).

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.21 (3H, t, J=7.06 Hz), 1.60 (3H, d, J=6.82 Hz), 3.58-3.59 (3H, m), 4.10-4.23 (2H, m), 4.73 (1H, q, J=6.82 Hz), 6.38 (1H, s), 6.74 (1H, d, J=2.52 Hz), 6.97 (1H, dd, J=9.21 Hz, 2.80 Hz), 7.43 (1H, d, J=9.29 Hz), 7.80 (1H, s).

Production Example 9

In a solution of 1.0 g of compound 5b dissolved in 10 ml of acetic acid was added 0.045 g of acetic anhydride, and the mixture was stirred at room temperature for 3 hours. A mixed solution of hexane:ethyl acetate=1:1 was then added, and the deposited crystals were collected by filtration and dried to give 1.16 g of compound 9a (the present compound 1-24).

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 2.10 (3H, s), 3.59 (3H, s), 6.39 (1H, s), 7.12 (1H, dd, J=8.80 Hz, 2.10 Hz), 7.29 (1H, bs), 7.44 (1H, d, J=8.82 Hz), 7.77 (1H, d, J=1.88 Hz), 7.81 (1H, s).

In a solution of 1.0 g of compound 9a dissolved in 10 ml of dimethylformamide was added 0.11 g of sodium hydride at room temperature, and the mixture was stirred for 10 minutes. Then, 0.43 g of methyl iodide was added at room temperature, and the mixture was left undisturbed for 3 days. The reaction mixture was then poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with water and then with diluted hydrochloric acid, and dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.36 g of compound 9b (the present compound 1-28).

m.p.: 207.2° C.

Production Example 10

According to the process as described above in Production Example 2, compound 10a (the present compound 1-75) was produced from 2-hydroxy-5-bromobenzaldehyde.

m.p.: 130.0° C.

To a solution of 1.85 g of compound 10a in 10 ml of N-methylpyrrolidone was added 0.67 g of copper (I) cyanide, and the mixture was heated and stirred at 170° C. to 180° C. for 6 hours. After cooling to room temperature, the reaction mixture was poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with cold ammonia water, with water, and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.85 g of compound 10b (the present compound 1-283).

m.p.: 174.3° C. (decomposition).

After 0.65 g of compound 10b was dissolved in 85% sulfuric acid, the solution was kept and stirred at 50° C. to 60° C. for 0.5 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.45 g of compound 10c (the present compound 1-293).

¹H-NMR (300 MHz, CDCl₃+DMSO, TMS, δ (ppm)): 3.60 (3H, s), 6.40 (1H, s), 7.58 (1H, d, J=8.76 Hz), 7.84-7.95 (3H, m).

First, 0.3 g of compound 10c was added to 10 ml of a solution of boron trifluoride methanol complex in methanol, and the mixture was heated and stirred at the reflux temperature for 7 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.22 g of compound 10d (the present compound 1-303).

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.59 (3H, m), 3.92 (3H, s), 6.40 (1H, s), 7.58 (1H, d, J=9.06 Hz), 7.89 (1H, s), 8.06-8.09 (2H, m).

Production Example 11

To a solution of 10.45 g of compound 11a, which had been produced according to the process as described in the JP-A 58-79960 publication, in 30 ml of N-methylpyrrolidone was added 4.56 g of copper (I) cyanide, and the mixture was kept and stirred at 110° C. to 120° C. for 6 hours. After cooling to room temperature, the reaction mixture was poured into water, which was extracted with t-butyl methyl ether. The organic layer was washed with cold ammonia water, with water, and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 5.14 g of compound [11b].

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.32 (3H, t, J=7.17 Hz), 4.31 (2H, q, J=7.22 Hz), 4.89 (2H, s), 7.70 (1H, d, J=1.82 Hz), 7.80 (1H, d, J=8.57 Hz), 7.93-7.95 (1H, m).

To a solution of 5.1 g of compound 11b in 50 ml of N,N-dimethylformamide was added 3.3 g of potassium carbonate, and the mixture was kept and stirred at 100° C. for 30 minutes. The reaction mixture was then cooled to room temperature and poured into water. The deposited crystals were collected by filtration. The crystals were washed with water and dried to give 4.0 g of compound 11c.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.46 (3H, t, J=7.24 Hz), 4.47 (2H, q, J=7.08 Hz), 5.30 (2H, bs), 7.69 (1H, d, J=8.67 Hz), 8.16 (1H, dd, J=8.76 Hz, 1.77 Hz), 8.34 (1H, d, J=1.87 Hz).

To a solution of 3.8 g of compound 11c in 50 ml of toluene was added 3.3 g of trichloromethyl chloroformate, and the mixture was heated and stirred at the reflux temperature of toluene for 1 hour. The reaction mixture was then concentrated to give a crude product of isocyanate.

To a suspension of 0.67 g of sodium hydride in 5 ml of N,N-dimethylformamide was added a solution of 3.1 g of ethyl 4,4,4-trifluoro-3-amino-crotonate in 5 ml of N,N-dimethylformamide below 10° C., and the mixture was stirred for 30 minutes. To the reaction mixture was then added dropwise a solution of the crude product of isocyanate obtained from compound 11c in 100 ml of tetrahydrofuran at −30° C. After completion of the dropwise addition, the mixture was warmed to room temperature and then stirred for 1 hour. To the reaction mixture was then added 4.3 g of methyl iodide, and the mixture was left undisturbed at room temperature overnight. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=2:1) to give 3.80 g of compound 11d as crystals.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.37 (3H, t, J=7.30 Hz), 3.36 (3H, m), 4.42 (2H, q, J=6.14 Hz), 6.14 (1H, s), 7.61 (1H, d, J=8.78 Hz), 8.26 (1H, dd, J=8.67 Hz, 2.12 Hz), 8.55 (1H, d, J=1.79 Hz).

First, 3.5 g of compound 11d was added to 20 ml of 85% sulfuric acid, and the mixture was kept and stirred at a temperature of 110° C. to 120° C. for 20 minutes. The reaction mixture was then poured into water, and the deposited crystals were collected by filtration and dried. The whole amount of the crystals obtained and 0.23 g of copper powder were added to 15 ml of quinoline, and the mixture was warmed to 120° C. to 130° C., at which temperature the mixture was kept and stirred for 1 hour. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2.5:1) to give 1.05 g of compound 11e (the present compound 1-282).

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.59-3.61 (3H, m), 6.42 (1H, s), 7.47 (1H, d, J=8.71 Hz), 8.11 (1H, s), 8.21 (1H, dd, J=8.79 Hz, 2.06 Hz), 8.48 (1H, d, J=1.85 Hz).

Production Example 12

According to the process as described in the JP-A 58-79960 publication, 2-bromo-4-fluoro-5-nitrophenol was obtained from 4-fluorophenol and then used as the starting material to produce compound 12a (the present compound 1-431) according to the process as described above in Production Example 11.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.61-3.62 (3H, m), 6.42 (1H, s), 7.24 (1H, d, J=10.4 Hz), 8.13 (1H, s), 8.33 (1H, d, J=5.79 Hz).

To a solution of 0.6 g of compound 12a in 9 ml of N,N-dimethylformamide was added 0.12 g of sodium methylsulfide below 0° C., and the mixture was stirred for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with water and then with diluted hydrochloric acid, dried over anhydrous magnesium sulfate, dried, and then concentrated. The crystals obtained were washed with t-butyl methyl ether to give 0.24 g of compound 12b (the present compound 1-201).

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 2.50 (s, 3H), 3.62 (3H, m), 6.43 (1H, s), 7.19 (1H, s), 8.07 (1H, s), 8.49 (1H, d, J=5.79 Hz).

Production Example 13

First, 1.0 g of compound 13a and 1.15 g of 3,4,5,6-tetrahydrophthalic anhydride were added to 15 ml of acetic acid, and the mixture was heated and stirred at the reflux temperature for 1 hour. The reaction mixture was concentrated under reduced pressure, and the residue was washed with hexane:isopropanol=1:1 (v/v) to give 1.48 g of compound 13b (the present compound 2-2001).

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.75-1.95 (4H, m), 2.35-2.55 (4H, m), 6.64 (1H, m), 7.01-7.15 (4H, m), 7.63 (1H, d, J=7.0 Hz).

Production Example 14

First, 0.2 g of compound 13a and 0.4 g of ethyl 3-{[1-(dimethylamino)-methylidene]amino}-4,4,4-trifluoro-2-butenoate were added to 5 ml of acetic acid, and the mixture was stirred at room temperature for 2 hours. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic, layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.05 g of compound 14a (the present compound 3-2001).

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 6.74 (1H, d, J=3.5 Hz), 7.00-7.06 (2H, m), 7.10 (1H, d, J=3.5 Hz), 7.21-7.32 (2H, m), 7.68 (1H, dd, J=1.8 Hz, 6.7 Hz), 8.40 (1H, s).

Production Example 15

To a solution of 1.5 g of compound 15a in 15 ml of acetic acid was added 1.9 g of 3,4,5,6-tetrahydrophthalic anhydride, and the mixture was heated at reflux for 6 hours. After cooling to room temperature, the reaction mixture was poured into ice water, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel column chromatography to give 3.0 g of compound 15b (the present compound 2-2004).

m.p.: 184.5° C.

Production Example 16

First, 25 g of compound 16a was added to 40 ml of thionyl chloride, and the mixture was heated and stirred at the reflux temperature for 4 hours. The reaction mixture was concentrated under reduced pressure, to which residue was added 100 ml of ethanol. To the reaction mixture was then added dropwise 14 ml of pyridine under ice cooling, and the mixture was stirred at room temperature for 2 days and then left undisturbed for a half day. The reaction mixture was then concentrated, to which diluted hydrochloric acid was added, and the mixture was extracted with ethyl acetate. The organic, layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated to give 27 g of compound 16b as a crude product.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.42 (3H, t, J=7.2 Hz), 2.66 (3H, s), 4.42 (2H, q, J=7.2 Hz), 7.43 (1H, d,.J=8.0 Hz), 8.15 (1H, dd, J=1.7 Hz, 8.0 Hz), 8.60 (1H, d, J=1.7 Hz).

First, 5.4 g of iron powder was added to a mixed solvent of 20 ml of acetic acid and 150 ml of water, and the mixture was heated to 70° C., to which a solution of 5.0 g of compound 16b in 20 ml of ethyl acetate was added dropwise. After completion of the dropwise addition, the mixture was left cooling to room temperature and stirred for 2 hours. Water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution, dried over anhydrous magnesium sulfate, and then concentrated to give 3.8 g of compound 16c as a crude product.

m.p.: 112.6° C.

To a solution of 1.0 g of compound 16c in 50 ml of acetic acid was added dropwise a solution of 0.42 g of sodium nitrite in 5 ml of water at 10° C. After completion of the dropwise addition, the mixture was left undisturbed at room temperature for a half day. Water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.5 g of compound 16d.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.44 (3H, t, J=7.1 Hz), 4.44 (2H, q, J=7.1 Hz), 7.78-7.89 (2H1, m), 8.16 (1H, d, J=1.1 Hz), 8.29 (1H, q, J=1.1 Hz).

To a solution of 1.0 g of compound 16d in 10 ml of N,N-dimethylformamide was added 0.2 g of sodium hydride at room temperature. After the gas evolution from the reaction mixture ceased, 1.0 g of o-(2,4-dinitrophenyl)hydroxylamine was added, and the mixture was stirred. After left undisturbed for 2 days, water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography to give 0.36 g of compound 16e.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.42 (3H, t, J=7.2 Hz), 4.41 (2H, q, J=7.2 Hz), 5.45 (2H, bs), 7.61-7.78 (2H, m), 7.86 (1H, s), 8.28 (1H, d, J=0.8 Hz).

First, 0.15 g of compound 16e and 0.12 g of 3,4,5,6-tetrahydrophthalic anhydride were dissolved in 10 ml of acetic acid, and the solution was heated and stirred at the reflux temperature for 1 hour. After the reaction mixture was left cooling to room temperature, water was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was washed with aqueous sodium hydrogencarbonate solution and then with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=3:1) to give 0.09 g of compound 16f (the present compound 2-2011).

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.42 (3H, t, J=7.2 Hz), 1.89 (4H, m), 2.50 (4H, m), 4.42 (2H, q, J=7.2 Hz), 7.79-7.84 (1H, m), 7.91-7.96 (1H, m), 8.03 (1H, m), 8.19 (1H, d, J=1.1 Hz).

Production Example 17

First, 300 mg of compound 16e and 230 mg of phenyl chloroformate were dissolved in 10 ml of tetrahydrofuran, to which 120 mg of pyridine was added at room temperature. After stirring at room temperature for 1 hour, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=2:1) to give 500 mg of compound 17a.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.45 (3H, t, J=7.1 Hz), 4.45 (2H, q, J=7.1 Hz), 7.15-7.42 (5H, m), 7.76-7.80 (1H, m), 7.89-7.94 (1H, m), 8.09 (1H, s), 8.27 (1H, s).

To a mixture of 280 mg of ethyl 4,4,4-trifluoro-3-aminochrotonate and 5 ml of N,N-dimethylformamide was added 60 mg of sodium hydride at room temperature, and the mixture was stirred for 10 minutes. To the reaction solution was added dropwise a solution of 500 mg of compound 17a in 6 ml of N,N-dimethylformamide. The mixture was stirred at 80° C. for 2 hours and then left cooling to room temperature, to which 500 mg of iodomethane was added. After stirring at room temperature for 4 hours, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and then concentrated. The residue was subjected to silica gel chromatography (eluent, hexane:ethyl acetate=5:2) to give 100 mg of compound 17b (the present compound 1-2068).

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.41 (3H, t, J=7.1 Hz), 3.59 (3H, m), 4.41 (2H, q, J=7.1 Hz), 6.44 (1H, s), 7.84 (1H, d, J=9.1 Hz), 7.93-7.97 (2H, m), 8.24 (1H, d, J=0.8 Hz).

Production Example 18

To a solution of 2.0 g of compound 3b and 1.2 g of pyridine in 10 ml of tetrahydrofuran was added dropwise a solution of 1.6 g of ClCO₂Et in 3ml of tetrahydrofuran at 0° C. to 10° C. After stirring at room temperature for 1 hour, diluted hydrochloric acid was added to the reaction mixture, which was extracted with ethyl acetate. The organic layer was concentrated, and the residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 2.7 g of compound 18a.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.37 (3H, t, J=7.2 Hz), 4.33 (2H, q, J=7.2 Hz), 7.26-7.34 (2H, m), 7.48-7.58 (2H, m), 8.17 (1H, d, J=4.1 Hz).

To 15 ml of N,N-dimethylformamide was added 0.5 g of sodium hydride, to which 2.4 g of H₂N(CF₃)C═CHCO₂Et was added dropwise under ice cooling. After stirring at room temperature for 30 minutes, a solution of compound 18a dissolved in 5 ml of N,N-dimethylformamide was added dropwise thereto. After heating at 100° C. for 4 hours and at 120° C. for 2 hours, the reaction mixture was cooled to room temperature. Then, 2.0 g of iodomethane was added, and the mixture was left standing overnight, to which diluted hydrochloric acid was added. The mixture was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 2.2 g of compound 18b (the present compound 1-875).

m.p.: 159.1° C.

Production Example 19

First, 1.3 g of potassium tert-butoxide and 0.9 g of acetohydroxamic acid were added to 25 ml of N,N-dimethylformamide, and the mixture was stirred at room temperature for 30 minutes. A solution of 1.5 g of compound 19a dissolved in 5 ml of N,N-dimethylformamide was added dropwise thereto, and the mixture was then left standing at room temperature overnight. To the reaction mixture was added aqueous sodium chloride solution, which was extracted with ethyl acetate. The organic layer was dried with magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=2:1) to give 0.8 g of compound 19b.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 4.38-4.64 (1H, br), 7.20-7.27 (2H, m), 7.43-7.47 (2H, m).

To 50 ml of toluene were added 2.1 g of compound 19b (produced in the same manner as described above) and 2.5 g of trichloromethyl chloroformate, and the mixture was heated at reflux for 2 hours. The reaction mixture was concentrated to give 2.5 g of compound 19c as a crude product.

To a suspension of 0.6 g of sodium hydride in 30 ml of N,N-dimethylformamide was added 2.7 g of ethyl 4,4,4-trifluoro-3-aminochrotonate at room temperature, and the mixture was stirred for 30 minutes. To the reaction mixture was then added dropwise a solution of the whole amount of the crude product of compound 19c dissolved in 50 ml of tetrahydrofuran at 0° C. After completion of the dropwise addition, the mixture was warmed to room temperature and stirred for 3 hours, to which 2.0 g of methyl iodide was added, and the mixture was left standing overnight. The reaction mixture was then poured into diluted hydrochloric acid, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 80 mg of compound 19d (the present compound 1-877).

¹H-NMR (250 MHz, CDCl₃, TMS,. δ (ppm)): 3.57 (3H, q, J=1.2 Hz), 6.41 (1H, s), 7.36 (1H, dd, J=1.6 Hz, 8.5 Hz), 7.45 (1H, d, J=8.5 Hz), 7.71 (1H, d, J=1.6 Hz).

Production Example 20

To a mixed solution of 190.0 g of compound 20a, 122.9 g of methyl chloroformate, and 150 ml of water was added dropwise aqueous sodium hydroxide solution (50 g of NaOH and 100 ml of H₂O) below 10° C. After completion of the dropwise addition, the mixture was stirred for 2 hours. The crystals obtained were then collected by filtration, washed with a solution (isopropyl alcohol:water=1:1), and dried to give 160.5 g of compound 20b.

Then, 160.0 g of compound 20b was dissolved in 250 ml of concentrated sulfuric acid, to which a mixed acid (42.5 g of fuming nitric acid and 30 ml of concentrated sulfuric acid) was added dropwise below 5° C. After completion of the dropwise addition, the mixture was stirred for 2 hours. The reaction mixture was poured into ice water, and the deposited crystals were collected by filtration, washed with water, and dried to give 186.5 g of compound 20c.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.98 (3H, s), 7.63 (1H, d, J=9.60 Hz), 8.03 (1H, d, J=6.83 Hz).

To 300 ml of water and 300 ml of ethanol was suspended 186.0 g of compound 20c, to which aqueous sodium hydroxide solution (60 g of NaOH and 120 ml of H₂O) was added dropwise at room temperature. After completion of the dropwise addition, the mixture was stirred for 1 hour and then concentrated to remove the ethanol. The residue obtained was made acidic by the addition of concentrated hydrochloric acid under ice cooling, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated to give 141.1 g of compound 20d.

According to the process as described in Production Example 2, compound 20e was produced from compound 20d.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.32 (3H, t, J=7.11 Hz), 4.30 (211, q, J=7.14 Hz), 4.77 (2H, s), 7.51 (1H, d, J=6.28 Hz), 7.58 (1H, d, J=9.81 Hz).

According to the process as described in Production Example 11, compound 20f was produced from compound 20e.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.33 (3H, t, J=7.12 Hz), 4.30 (2H, q, J=7.12 Hz), 4.86 (2H, s), 7.52 (1H, d, J=5.66 Hz), 7.59 (1H, d, J=9.39 Hz).

First, 30 g of compound 20f was dissolved in 30 ml of N,N-dimethylformamide, to which 18.4 g of sodium acetate and 3 ml of water were added, and the mixture was kept and stirred at a temperature of 80° C. to 90° C. for 9 hours. After cooling to room temperature, diluted hydrochloric acid was poured into the reaction mixture, which was extracted with ethyl acetate. The organic layer was dried over magnesium sulfate and then concentrated. The residue was subjected to silica gel column chromatography (eluent, hexane:ethyl acetate=3:1) to give 13.6 g of compound 20 g.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm): 1.32 (3H, t, J=7.08 Hz), 4.29 (2H, q, J=7.08 Hz), 4.79 (2H, s), 7.48 (1H, s), 7.56 (1H, s).

First, 13 g of compound 20 g was dissolved in 40 ml of N,N-dimethylformamide, to which 7.3 g of potassium carbonate was added at room temperature. Then, 6.2 g of dimethylsulfuric acid was added at 30° C. to 40° C. thereto, and the mixture was stirred for 30 minutes. The reaction mixture was then poured into water, which was extracted with ethyl acetate. The organic layer was washed with diluted hydrochloric acid, dried over magnesium sulfate, and then concentrated. The crystals obtained were washed with a solution (t-butyl methyl ether:hexane=1:2) to give 10.7 g of compound 20h.

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.31 (3H, t, J=7.16 Hz), 4.00 (3H, s), 4.29 (2H, q, J=7.16 Hz), 4.78 (2H, s), 7.32 (1H, s), 7.34 (1H, s).

According to the process as described in Production Example 11, compound 20i was produced from compound 20h.

According to the process as described in Production Example 11, compound 20j (the present compound 1-86) was produced from compound 20i.

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.61 (3H, m), 3.95 (3H, s), 6.42 (1H, s), 6.89 (1H, s), 8.00 (1H, s), 8.09 (1H, s).

Examples of the present compounds are shown below together with their compound numbers.

Compounds of the general formula:

TABLE 1

Compound R² R³ R⁴ A Y 1-1  H H H CH O 1-2  Cl H Cl CH O 1-3  H H H CH S 1-4  Cl H H CH O 1-5  OCH₃ H H CH O 1-6  NO₂ H H CH O 1-7  NH₂ H H CH O 1-8  NHCH₃ H H CH O 1-9  N(CH₃)₂ H H CH O 1-10 NHSO₂CH₃ H H CH O 1-11 NHCH(CH₃)CO₂Et H H CH O 1-12 NHCH(CH₃)CO₂Et H Cl CH O 1-13 N(CH₃)CH(CH₃)CO₂Et H Cl CH O 1-14 N(CH₃)SO₂CH₃ H Cl CH O 1-15 NHSO₂CH₃ H Cl CH O 1-16 NHCH(CH₃)CO₂Et Cl H CH O 1-17 N(CH₃)CH(CH₃)CO₂Et Cl H CH O

TABLE 2 Compound R² R³ R⁴ A Y 1-18 N(CH₃SO₂CH₃ Cl H CH O 1-19 NHSO₂CH₃ Cl H CH O 1-20 NO₂ H Cl CH O 1-21 NH₂ H Cl CH O 1-22 NO₂ Cl H CH O 1-23 NH₂ Cl H CH O 1-24 NHCOCH₃ H H CH O 1-25 NHCOCF₃ H H CH O 1-26 NHSO₂Et H H CH O 1-27 NHSO₂CH₂Cl H H CH O 1-28 N(CH₃)COCH₃ H H CH O 1-29 N(CH₃)COCF₃ H H CH O 1-30 N(CH₃)SO₂Et H H CH O 1-31 CO₂C(CH₃)₂CO₂Et H H CH O 1-32 N(CH₃)SO₂CH₂Cl H H CH O 1-33 NHCOCH₃ H Cl CH O 1-34 NHCOCF₃ H Cl CH O 1-35 NHSO₂Et H Cl CH O 1-36 NHSO₂CH₂Cl H Cl CH O 1-37 N(CH₃)COCH₃ Cl H CH O 1-38 N(CH₃)COCF₃ Cl H CH O 1-39 N(CH₃)SO₂Et Cl H CH O 1-40 N(CH₃)SO₂CH₂Cl Cl H CH O 1-42 NHCH₂CO₂Me H H CH O 1-43 NHCH₂CO₂Et H H CH O

TABLE 3 Compound R² R³ R⁴ A Y 1-44 NHCH(CH₃)COOH H H CH O 1-45 NHCH(CH₃)CONH₂ H H CH O 1-46 NHCH(CH₃)CONHCH₃ H H CH O 1-47 NHCH₂CO₂Me H Cl CH O 1-48 NHCH₂CO₂Et H Cl CH O 1-49 NHCH(CH₃)COOH H Cl CH O 1-50 NHCH(CH₃)CONH₂ H Cl CH O 1-51 NHCH(CH₃)CONHCH₃ H Cl CH O 1-52 NHCH₂CO₂Me Cl H CH O 1-53 NHCH₂CO₂Et Cl H CH O 1-54 NHCH(CH₃)COOH Cl H CH O 1-55 NHCH(CH₃)CONH₂ Cl H CH O 1-56 NHCH(CH₃)CONHCH₃ Cl H CH O 1-57 NHCH₂CH₂CH₃ H H CH O 1-58 NHCH₂CH═CH₂ H H CH O 1-59 NHCH₂C≡CH H H CH O 1-60 N(CH₃)CH₂CH₂CH₃ H H CH O 1-61 N(CH₃)CH₂CH═CH₂ H H CH O 1-62 N(CH₃)CH₂C≡CH H H CH O 1-63 NHCH₂CH₂CH₃ H Cl CH O 1-64 NHCH₂CH═CH₂ H Cl CH O 1-65 NHCH₂C≡CH H Cl CH O 1-66 N(CH₃)CH₂CH₂CH₃ H Cl CH O 1-67 N(CH₃)CH₂CH═CH₂ H Cl CH O 1-68 N(CH₃)CH₂C≡CH H Cl CH O

TABLE 4 Compound R² R³ R⁴ A Y 1-69 NHCH₂CH₂CH₃ Cl H CH O 1-70 NHCH₂CH═CH₂ Cl H CH O 1-71 NHCH₂C≡CH Cl H CH O 1-72 N(CH₃)CH₂CH₂CH₃ Cl H CH O 1-73 N(CH₃)CH₂CH═CH₂ Cl H CH O 1-74 N(CH₃)CH₂C≡CH Cl H CH O 1-75 Br H H CH O 1-76 Br H Cl CH O l-77 Br Cl H CH O 1-78 OH H H CH O 1-79 OH H Cl CH O 1-80 OH Cl H CH O 1-81 OH H NO₂ CH O 1-82 OH NO₂ H CH O 1-83 OCH₃ H Cl CH O 1-84 OCH₃ Cl H CH O 1-85 OCH₃ H NO₂ CH O 1-86 OCH₃ NO₂ H CH O 1-87 OCH(CH₃)CH₃ H H CH O 1-88 OCH(CH₃)CH₃ H Cl CH O 1-89 OCH(CH₃)CH₃ Cl H CH O 1-90 OCH(CH₃)CH₃ H NO₂ CH O 1-91 OCH(CH₃)CH₃ NO₂ H CH O 1-92 OCH₂CH═CH₂ H H CH O 1-93 OCH₂CH═CH₂ H Cl CH O

TABLE 5 Compound R² R³ R⁴ A Y 1-94 OCH₂CH═CH₂ Cl H CH O 1-95 OCH₂CH═CH₂ H NO₂ CH O 1-96 OCH₂CH═CH₂ NO₂ H CH O 1-97 OCH(CH₃)CH═CH₂ H H CH O 1-98 OCH(CH₃)CH═CH₂ H Cl CH O 1-99 OCH(CH₃)CH═CH₂ Cl H CH O 1-100 OCH(CH₃)CH═CH₂ H NO₂ CH O 1-101 OCH(CH₃)CH═CH₂ NO₂ H CH O 1-102 OCH₂C(Cl)═CH₂ H H CH O 1-103 OCH₂C(Cl)═CH₂ H Cl CH O 1-104 OCH₂C(Cl)═CH₂ Cl H CH O 1-105 OCH₂C(Cl)═CH₂ H NO₂ CH O 1-106 OCH₂C(Cl)═CH₂ NO₂ H CH O 1-107 OCH₂C≡CH H H CH O 1-108 OCH₂C≡CH H Cl CH O 1-109 OCH₂C≡CH Cl H CH O 1-110 OCH₂C≡CH H NO₂ CH O 1-111 OCH₂C≡CH NO₂ H CH O 1-112 OCH(CH₃)C≡CH H H CH O 1-113 OCH(CH₃)C≡CH H Cl CH O 1-114 OCH(CH₃)C≡CH Cl H CH O 1-115 OCH(CH₃)C≡CH H NO₂ CH O 1-116 OCH(CH₃)C≡CH NO₂ H CH O 1-117 OCH(CH₃)COOH H H CH O 1-118 OCH(CH₃)COOH H Cl CH O

TABLE 6 Compound R² R³ R⁴ A Y 1-119 OCH(CH₃)COOH Cl H CH O 1-120 OCH(CH₃)COOH H NO₂ CH O 1-121 OCH(CH₃)COOH NO₂ H CH O 1-122 OCH(CH₃)COOMe H H CH O 1-123 OCH(CH₃)COOMe H Cl CH O 1-124 OCH(CH₃)COOMe Cl H CH O 1-125 OCH(CH₃)COOMe H NO₂ CH O 1-126 OCH(CH₃)COOMe NO₂ H CH O 1-127 OCH(CH₃)COOEt H H CH O 1-128 OCH(CH₃)COOEt H Cl CH O 1-129 OCH(CH₃)COOEt Cl H CH O 1-130 OCH(CH₃)COOEt H NO₂ CH O 1-131 OCH(CH₃)COOEt NO₂ H CH O 1-132 OCH(CH₃)COOPr H H CH O 1-133 OCH(CH₃)COOPr H Cl CH O 1-134 OCH(CH₃)COOPr Cl H CH O 1-135 OCH(CH₃)COOPr H NO₂ CH O 1-136 OCH(CH₃)COOPr NO₂ H CH O 1-137 OCH(CH₃)COO-i-Pr H H CH O 1-138 OCH(CH₃)COO-i-Pr H Cl CH O 1-139 OCH(CH₃)COO-i-Pr Cl H CH O 1-140 OCH(CH₃)COO-i-Pr H NO₂ CH O 1-141 OCH(CH₃)COO-i-Pr NO₂ H CH O 1-142 OCH(CH₃)COOBu H H CH O 1-143 OCH(CH₃)COOBu H Cl CH O

TABLE 7 Compound R² R³ R⁴ A Y 1-144 OCH(CH₃)COOBu Cl H CH O 1-145 OCH(CH₃)COOBu H NO₂ CH O 1-146 OCH(CH₃)COOBu NO₂ H CH O 1-147 OCH(CH₃)COOPen H H CH O 1-148 OCH(CH₃)COOPen H Cl CH O 1-149 OCH(CH₃)COOPen Cl H CH O 1-150 OCH(CH₃)COOPen H NO₂ CH O 1-151 OCH(CH₃)COOPen NO₂ H CH O 1-152 OCH(CH₃)COO-c-Pen H H CH O 1-153 OCH(CH₃)COO-c-Pen H Cl CH O 1-154 OCH(CH₃)COO-c-Pen Cl H CH O 1-155 OCH(CH₃)COO-c-Pen H NO₂ CH O 1-156 OCH(CH₃)COO-c-Pen NO₂ H CH O 1-157 OCH(CH₃)COOHex H H CH O 1-158 OCH(CH₃)COOHex H Cl CH O 1-159 OCH(CH₃)COOHex Cl H CH O 1-160 OCH(CH₃)COOHex H NO₂ CH O 1-161 OCH(CH₃)COOHex NO₂ H CH O 1-162 OCH(CH₃)COO-c-Hex H H CH O 1-163 OCH(CH₃)COO-c-Hex H Cl CH O 1-164 OCH(CH₃)COO-c-Hex Cl H CH O 1-165 OCH(CH₃)COO-c-Hex H NO₂ CH O 1-166 OCH(CH₃)COO-c-Hex NO₂ H CH O 1-167 OCH(CH₃)CO₂CH₂CO₂H H H CH O 1-168 OCH(CH₃)CO₂CH₂CO₂H H Cl CH O

TABLE 8 Com- pound R² R³ R⁴ A Y 1-169 OCH(CH₃)CO₂CH₂CO₂H Cl H CH O 1-170 OCH(CH₃)CO₂CH₂CO₂H H NO₂ CH O 1-171 OCH(CH₃)CO₂CH₂CO₂H NO₂ H CH O 1-172 OCH(CH₃)CO₂CH₂CO₂Me H H CH O 1-173 OCH(CH₃)CO₂CH₂CO₂Me H Cl CH O 1-174 OCH(CH₃)CO₂CH₂CO₂Me Cl H CH O 1-175 OCH(CH₃)CO₂CH₂CO₂Me H NO₂ CH O 1-176 OCH(CH₃)CO₂CH₂CO₂Me NO₂ H CH O 1-177 OCH(CH₃)CO₂CH₂CO₂Et H H CH O 1-178 OCH(CH₃)CO₂CH₂CO₂Et H Cl CH O 1-179 OCH(CH₃)CO₂CH₂CO₂Et Cl H CH O 1-180 OCH(CH₃)CO₂CH₂CO₂Et H NO₂ CH O 1-181 OCH(CH₃)CO₂CH₂CO₂Et NO₂ H CH O 1-182 OCH(CH₃)CO₂CH(CH₃)CO₂H H H CH O 1-183 OCH(CH₃)CO₂CH(CH₃)CO₂H H Cl CH O 1-184 OCH(CH₃)CO₂CH(CH₃)CO₂H Cl H CH O 1-185 OCH(CH₃)CO₂CH(CH₃)CO₂H H NO₂ CH O 1-186 OCH(CH₃)CO₂CH(CH₃)CO₂H NO₂ H CH O 1-187 OCH(CH₃)CO₂CH(CH₃)CO₂Me H H CH O 1-188 OCH(CH₃)CO₂CH(CH₃)CO₂Me H Cl CH O 1-189 OCH(CH₃)CO₂CH(CH₃)CO₂Me Cl H CH O 1-190 OCH(CH₃)CO₂CH(CH₃)CO₂Me H NO₂ CH O 1-191 OCH(CH₃)CO₂CH(CH₃)CO₂Me NO₂ H CH O 1-192 OCH(CH₃)CO₂CH(CH₃)CO₂Et H H CH O 1-193 OCH(CH₃)CO₂CH(CH₃)CO₂Et H Cl CH O

TABLE 9 Com- pound R² R³ R⁴ A Y 1-194 OCH(CH₃)CO₂CH(CH₃)CO₂Et Cl H CH O 1-195 OCH(CH₃)CO₂CH(CH₃)CO₂Et H NO₂ CH O 1-196 OCH(CH₃)CO₂CH(CH₃)CO₂Et NO₂ H CH O 1-197 SCH₃ H H CH O 1-198 SCH₃ H Cl CH O 1-199 SCH₃ Cl H CH O 1-200 SCH₃ H NO₂ CH O 1-201 SCH₃ NO₂ H CH O 1-202 SCH(CH₃)CH₃ H H CH O 1-203 SCH(CH₃)CH₃ H Cl CH O 1-204 SCH(CH₃)CH₃ Cl H CH O 1-205 SCH(CH₃)CH₃ H NO₂ CH O 1-206 SCH(CH₃)CH₃ NO₂ H CH O 1-207 SCHCH═CH₂ H H CH O 1-208 SCHCH═CH₂ H Cl CH O 1-209 SCHCH═CH₂ Cl H CH O 1-210 SCHCH═CH₂ H NO₂ CH O 1-211 SCHCH═CH₂ NO₂ H CH O 1-212 SCHC≡CH H H CH O 1-213 SCHC≡CH H Cl CH O 1-214 SCHC≡CH Cl H CH O 1-215 SCHC≡CH H NO₂ CH O 1-216 SCHC≡CH NO₂ H CH O 1-217 SCH₂COOH H H CH O 1-218 SCH₂COOH H Cl CH O

TABLE 10 Compound R² R³ R⁴ A Y 1-219 SCH₂COOH Cl H CH O 1-220 SCH₂COOH H NO₂ CH O 1-221 SCH₂COOH NO₂ H CH O 1-222 SCH₂COOMe H H CH O 1-223 SCH₂COOMe H Cl CH O 1-224 SCH₂COOMe Cl H CH O 1-225 SCH₂COOMe H NO₂ CH O 1-226 SCH₂COOMe NO₂ H CH O 1-227 SCH₂COOEt H H CH O 1-228 SCH₂COOEt H Cl CH O 1-229 SCH₂COOEt Cl H CH O 1-230 SCH₂COOEt H NO₂ CH O 1-231 SCH₂COOEt NO₂ H CH O 1-232 SCH(CH₃)COOH H H CH O 1-233 SCH(CH₃)COOH H Cl CH O 1-234 SCH(CH₃)COOH Cl H CH O 1-235 SCH(CH₃)COOH H NO₂ CH O 1-236 SCH(CH₃)COOH NO₂ H CH O 1-237 SCH(CH₃)COOMe H H CH O 1-238 SCH(CH₃)COOMe H Cl CH O 1-239 SCH(CH₃)COOMe Cl H CH O 1-240 SCH(CH₃)COOMe H NO₂ CH O 1-241 SCH(CH₃)COOMe NO₂ H CH O 1-242 SCH(CH₃)COOEt H H CH O 1-243 SCH(CH₃)COOEt H Cl CH O

TABLE 11 Com- pound R² R³ R⁴ A Y 1-244 SCH(CH₃)COOEt Cl H CH O 1-245 SCH(CH₃)COOEt H NO₂ CH O 1-246 SCH(CH₃)COOEt NO₂ H CH O 1-247 SCH(CH₃)COO-i-Pr H H CH O 1-248 SCH(CH₃)COO-i-Pr H Cl CH O 1-249 SCH(CH₃)COO-i-Pr Cl H CH O 1-250 SCH(CH₃)COO-i-Pr H NO₂ CH O 1-251 SCH(CH₃)COO-i-Pr NO₂ H CH O 1-252 SCH(CH₃)CO₂CH₂CO₂H H H CH O 1-253 SCH(CH₃)CO₂CH₂CO₂H H Cl CH O 1-254 SCH(CH₃)CO₂CH₂CO₂H Cl H CH O 1-255 SCH(CH₃)CO₂CH₂CO₂H H NO₂ CH O 1-256 SCH(CH₃)CO₂CH₂CO₂H NO₂ H CH O 1-257 SCH(CH₃)CO₂CH₂CO₂Me H H CH O 1-258 SCH(CH₃)CO₂CH₂CO₂Me H Cl CH O 1-259 SCH(CH₃)CO₂CH₂CO₂Me Cl H CH O 1-260 SCH(CH₃)CO₂CH₂CO₂Me H NO₂ CH O 1-261 SCH(CH₃)CO₂CH₂CO₂Me NO₂ H CH O 1-262 SCH(CH₃)CO₂CH₂CO₂Et H H CH O 1-263 SCH(CH₃)CO₂CH₂CO₂Et H Cl CH O 1-264 SCH(CH₃)CO₂CH₂CO₂Et Cl H CH O 1-265 SCH(CH₃)CO₂CH₂CO₂Et H NO₂ CH O 1-266 SCH(CH₃)CO₂CH₂CO₂Et NO₂ H CH O 1-267 SCH(CH₃)CO₂CH(CH₃)CO₂H H H CH O 1-268 SCH(CH₃)CO₂CH(CH₃)CO₂H H Cl CH O

TABLE 12 Com- pound R² R³ R⁴ A Y 1-269 SCH(CH₃)CO₂CH(CH₃)CO₂H Cl H CH O 1-270 SCH(CH₃)CO₂CH(CH₃)CO₂H H NO₂ CH O 1-271 SCH(CH₃)CO₂CH(CH₃)CO₂H NO₂ H CH O 1-272 SCH(CH₃)CO₂CH(CH₃)CO₂Me H H CH O 1-273 SCH(CH₃)CO₂CH(CH₃)CO₂Me H Cl CH O 1-274 SCH(CH₃)CO₂CH(CH₃)CO₂Me Cl H CH O 1-275 SCH(CH₃)CO₂CH(CH₃)CO₂Me H NO₂ CH O 1-276 SCH(CH₃)CO₂CH(CH₃)CO₂Me NO₂ H CH O 1-277 SCH(CH₃)CO₂CH(CH₃)CO₂Et H H CH O 1-278 SCH(CH₃)CO₂CH(CH₃)CO₂Et H Cl CH O 1-279 SCH(CH₃)CO₂CH(CH₃)CO₂Et Cl H CH O 1-280 SCH(CH₃)CO₂CH(CH₃)CO₂Et H NO₂ CH O 1-281 SCH(CH₃)CO₂CH(CH₃)CO₂Et NO₂ H CH O 1-282 H NO₂ H CH O 1-283 C≡N H H CH O 1-284 C≡N H Cl CH O 1-285 C≡N Cl H CH O 1-286 C≡N H NO₂ CH O 1-287 C≡N NO₂ H CH O 1-288 C(═O)H H H CH O 1-289 C(═O)H H Cl CH O 1-290 C(═O)H Cl H CH O 1-291 C(═O)H H NO₂ CH O 1-292 C(═O)H NO₂ H CH O 1-293 C(═O)NH₂ H H CH O

TABLE 13 Compound R² R³ R⁴ A Y 1-294 C(═O)NH₂ H Cl CH O 1-295 C(═O)NH₂ Cl H CH O 1-296 C(═O)NH₂ H NO₂ CH O 1-297 C(═O)NH₂ NO₂ H CH O 1-298 CO₂H H H CH O 1-299 CO₂H H Cl CH O 1-300 CO₂H Cl H CH O 1-301 CO₂H H NO₂ CH O 1-302 CO₂H NO₂ H CH O 1-303 CO₂Me H H CH O 1-304 CO₂Me H Cl CH O 1-305 CO₂Me Cl H CH O 1-306 CO₂Me H NO₂ CH O 1-307 CO₂Me NO₂ H CH O i-308 CO₂Et H H CH O 1-309 CO₂Et H Cl CH O 1-310 CO₂Et Cl H CH O 1-311 CO₂Et H NO₂ CH O 1-312 CO₂Et NO₂ H CH O 1-313 CO₂CH₂CO₂H H H CH O 1-314 CO₂CH₂CO₂H H Cl CH O 1-315 CO₂CH₂CO₂H Cl H CH O 1-316 CO₂CH₂CO₂H H NO₂ CH O 1-317 CO₂CH₂CO₂H NO₂ H CH O 1-318 CO₂CH₂CO₂Me H H CH O

TABLE 14 Compound R² R³ R⁴ A Y 1-319 CO₂CH₂CO₂Me H Cl CH O 1-320 CO₂CH₂CO₂Me Cl H CH O 1-321 CO₂CH₂CO₂Me H NO₂ CH O 1-322 CO₂CH₂CO₂Me NO₂ H CH O 1-323 CO₂CH₂CO₂Et H H CH O 1-324 CO₂CH₂CO₂Et H Cl CH O 1-325 CO₂CH₂CO₂Et Cl H CH O 1-326 CO₂CH₂CO₂Et H NO₂ CH O 1-327 CO₂CH₂CO₂Et NO₂ H CH O 1-328 CO₂CH(CH₃)CO₂H H H CH O 1-329 CO₂CH(CH₃)CO₂H H Cl CH O 1-330 CO₂CH(CH₃)CO₂H Cl H CH O 1-331 CO₂CH(CH₃)CO₂H H NO₂ CH O 1-332 CO₂CH(CH₃)CO₂H NO₂ H CH O 1-333 CO₂CH(CH₃)CO₂Me H H CH O 1-334 CO₂CH(CH₃)CO₂Me H Cl CH O 1-335 CO₂CH(CH₃)CO₂Me Cl H CH O 1-336 CO₂CH(CH₃)CO₂Me H NO₂ CH O 1-337 CO₂CH(CH₃)CO₂Me NO₂ H CH O 1-338 CO₂CH(CH₃)CO₂Et H H CH O 1-339 CO₂CH(CH₃)CO₂Et H Cl CH O 1-340 CO₂CH(CH₃)CO₂Et Cl H CH O 1-341 CO₂CH(CH₃)CO₂Et H NO₂ CH O 1-342 CO₂CH(CH₃)CO₂Et NO₂ H CH O 1-343 CO₂C(CH₃)₂CO₂H H H CH O

TABLE 15 Compound R² R³ R⁴ A Y 1-344 CO₂C(CH₃)₂CO₂H H Cl CH O 1-345 CO₂C(CH₃)₂CO₂H Cl H CH O 1-346 CO₂C(CH₃)₂CO₂H H NO₂ CH O 1-347 CO₂C(CH₃)₂CO₂H NO₂ H CH O 1-348 CO₂C(CH₃)₂CO₂Me H H CH O 1-349 CO₂C(CH₃)₂CO₂Me H Cl CH O 1-350 CO₂C(CH₃)₂CO₂Me Cl H CH O 1-351 CO₂C(CH₃)₂CO₂Me H NO₂ CH O 1-352 CO₂C(CH₃)₂CO₂Me NO₂ H CH O 1-353 CO₂C(CH₃)₂CO₂Et H Cl CH O 1-354 CO₂C(CH₃)₂CO₂Et Cl H CH O 1-355 CO₂C(CH₃)₂CO₂Et H NO₂ CH O 1-356 CO₂C(CH₃)₂CO₂Et NO₂ H CH O 1-357 CH₃ H H CH O 1-358 CH₃ H Cl CH O 1-359 CH₃ GI H CH O 1-360 CH₃ H NO₂ CH O 1-361 CH₃ NO₂ H CH O 1-362 CF₃ H H CH O 1-363 CF₃ H Cl CH O 1-364 CF₃ Cl H CH O 1-365 CF₃ H NO₂ CH O 1-366 CF₃ NO₂ H CH O 1-367 CH═CHCO₂H H H CH O

TABLE 16 Compound R² R³ R⁴ A Y 1-368 CH═CHCO₂H H Cl CH O 1-369 CH═CHCO₂H Cl H CH O 1-370 CH═CHCO₂H H NO₂ CH O 1-371 CH═CHCO₂H NO₂ H CH O 1-372 CH═CHCO₂Me H H CH O 1-373 CH═CHCO₂Me H Cl CH O 1-374 CH═CHCO₂Me Cl H CH O 1-375 CH═CHCO₂Me H NO₂ CH O 1-376 CH═CHCO₂Me NO₂ H CH O 1-377 CH═CHCO₂Et H H CH O 1-378 CH═CHCO₂Et H Cl CH O 1-379 CH═CHCO₂Et Cl H CH O 1-380 CH═CHCO₂Et H NO₂ CH O 1-381 CH═CHCO₂Et NO₂ H CH O 1-382 CH₂CH₂CO₂H H H CH O 1-383 CH₂CH₂CO₂H H Cl CH O 1-384 CH₂CH₂CO₂H Cl H CH O 1-385 CH₂CH₂CO₂H H NO₂ CH O 1-386 CH₂CH₂CO₂H NO₂ H CH O 1-387 CH₂CH₂CO₂Me H H CH O 1-388 CH₂CH₂CO₂Me H Cl CH O 1-389 CH₂CH₂CO₂Me Cl H CH O 1-390 CH₂CH₂CO₂Me H NO₂ CH O 1-391 CH₂CH₂CO₂Me NO₂ H CH O 1-392 CH₂CH₂CO₂Et H H CH O

TABLE 17 Compound R² R³ R⁴ A Y 1-393 CH₂CH₂CO₂Et H Cl CH O 1-394 CH₂CH₂CO₂Et Cl H CH O 1-395 CH₂CH₂CO₂Et H NO₂ CH O 1-396 CH₂CH₂CO₂Et NO₂ H CH O 1-397 CH₂CH(Cl)CO₂H H H CH O 1-398 CH₂CH(Cl)CO₂H H Cl CH O 1-399 CH₂CH(Cl)CO₂H Cl H CH O 1-400 CH₂CH(Cl)CO₂H H NO₂ CH O 1-401 CH₂CH(Cl)CO₂H NO₂ H CH O 1-402 CH₂CH(Cl)CO₂Me H H CH O 1-403 CH₂CH(Cl)CO₂Me H Cl CH O 1-404 CH₂CH(Cl)CO₂Me Cl H CH O 1-405 CH₂CH(Cl)CO₂Me H NO₂ CH O 1-406 CH₂CH(Cl)CO₂Me NO₂ H CH O 1-407 CH₂CH(Cl)CO₂Et H H CH O 1-408 CH₂CH(Cl)CO₂Et H Cl CH O 1-409 CH₂CH(Cl)CO₂Et Cl H CH O 1-410 CH₂CH(Cl)CO₂Et H NO₂ CH O 1-411 CH₂CH(Cl)CO₂Et NO₂ H CH O 1-412 C(═O)CH₃ H H CH O 1-413 C(═O)CH₃ H Cl CH O 1-414 C(═O)CH₃ Cl H CH O 1-415 C(═O)CH₃ H NO₂ CH O l-416 C(═O)CH₃ NO₂ H CH O 1-417 C(CH₃)═NOH H H CH O

TABLE 18 Compound R² R³ R⁴ A Y 1-418 C(CH₃)═NOH H Cl CH O 1-419 C(CH₃)═NOH Cl H CH O 1-420 C(CH₃)═NOH H NO₂ CH O 1-421 C(CH₃)═NOH NO₂ H CH O 1-422 C(CH₃)═NOMe H H CH O 1-423 C(CH₃)═NOMe H Cl CH O 1-424 C(CH₃)═NOMe Cl H CH O 1-425 C(CH₃)═NOMe H NO₂ CH O 1-426 C(CH₃)═NOMe NO₂ H CH O 1-427 F H H CH O 1-428 F H Cl CH O 1-429 F Cl H CH O 1-430 F H NO₂ CH O 1-431 F NO₂ H CH O 1-432 Cl H Cl CH S 1-433 Cl H H CH S 1-434 OCH₃ H H CH S 1-435 NO₂ H H CH S 1-436 NH₂ H H CH S 1-437 NHCH₃ H H CH S 1-438 N(CH₃)₂ H H CH S 1-439 NHSO₂CH₃ H H CH S 1-440 NHCH(CH₃)CO₂Et H H CH S 1-441 NHCH(CH₃)CO₂Et H Cl CH S 1-442 N(CH₃)CH(CH₃)CO₂Et H Cl CH S

TABLE 19 Compound R² R³ R⁴ A Y 1-443 N(CH₃)SO₂CH₃ H Cl CH S 1-444 NHSO₂CH₃ H Cl CH S 1-445 NHCH(CH₃)CO₂Et Cl H CH S 1-446 N(CH₃)CH(CH₃)CO₂Et Cl H CH S 1-447 N(CH₃)SO₂CH₃ Cl H CH S 1-448 NHSO₂CH₃ Cl H CH S 1-449 NO₂ H Cl CH S 1-450 NH₂ H Cl CH S 1-451 NO₂ Cl H CH S 1-452 NH₂ Cl H CH S 1-453 NHCOCH₃ H H CH S 1-454 NHCOCF₃ H H CH S 1-455 NHSO₂Et H H CH S 1-456 NHSO₂CH₂Cl H H CH S 1-457 N(CH₃)COCH₃ H H CH S 1-458 N(CH₃)COCF₃ H H CH S 1-459 N(CH₃)SO₂Et H H CH S 1-460 N(CH)SO₂CH₂Cl H H CH S 1-461 NHCOCH₃ H Cl CH S 1-462 NHCOCF₃ H Cl CH S 1-463 NHSO₂Et H Cl CH S 1-464 NHSO₂CH₂Cl H Cl CH S 1-465 N(CH₃)COCH₃ Cl H CH S 1-466 N(CH₃)COCF₃ Cl H CH S 1-467 N(CH₃)SO₂Et Cl H CH S

TABLE 20 Compound R² R³ R⁴ A Y 1-468 N(CH₃)SO₂CH₂Cl Cl H CH S 1-469 NHCH₂CO₂Me H H CH S 1-470 NHCH₂CO₂Et H H CH S 1-471 NHCH(CH₃)COOH H H CH S 1-472 NHCH(CH₃)CONH₂ H H CH S 1-473 NHCH(CH₃)CONHCH₃ H H CH S 1-474 NHCH₂CO₂Me H Cl CH S 1-475 NHCH₂CO₂Et H Cl CH S 1-476 NHCH(CH₃)COOH H Cl CH S 1-477 NHCH(CH₃)CONH₂ H Cl CH S 1-478 NHCH(CH₃)CONHCH₃ H Cl CH S 1-479 NHCH₂CO₂Me Cl H GH S 1-480 NHCH₂CO₂Et Cl H CH S 1-481 NHCH(CH₃)COOH Cl H CH S 1-482 NHCH(CH₃)CONH₂ Cl H CH S 1-483 NHCH(CH₃)CONHCH₃ Cl H CH S 1-484 NHCH₂CH₂CH₃ H H CH S 1-485 NHCH₂CH═CH₂ H H CH S 1-486 NHCH₂C≡CH H H CH S 1-487 N(CH₃)CH₂CH₂CH₃ H H CH S 1-488 N(CH₃)CH₂CH═CH₂ H H CH S 1-489 N(CH₃)CH₂C≡CH H H CH S 1-490 NHCH₂CH₂CH₃ H Cl CH S 1-491 NHCH₂CH═CH₂ H Cl CH S 1-492 NHCH₂C≡CH H Cl CH S

TABLE 21 Compound R² R³ R⁴ A Y 1-493 N(CH₃)CH₂CH₂CH₃ H Cl CH S 1-494 N(CH₃)CH₂CH═CH₂ H Cl CH S 1-495 N(CH₃)CH₂C≡CH H Cl CH S 1-496 NHCH₂CH₂CH₃ Cl H CH S 1-497 NHCH₂CH═CH₂ Cl H CH S 1-498 NHCH₂C≡CH Cl H CH S 1-499 N(CH₃)CH₂CH₂CH₃ Cl H CH S 1-500 N(CH₃)CH₂CH═CH₂ Cl H CH S 1-501 N(CH₃)CH₂C≡CH Cl H CH S 1-502 Br H H CH S 1-503 Br H Cl CH S 1-504 Br Cl H CH S 1-505 OH H H CH S 1-506 OH H Cl CH S 1-507 OH Cl H CH S 1-508 OH H NO₂ CH S 1-509 OH NO₂ H CH S 1-510 OCH₃ H Cl CH S 1-511 OCH₃ Cl H CH S 1-512 OCH₃ H NO₂ CH S 1-513 OCH₃ NO₂ H CH S 1-514 OCH(CH₃)CH₃ H H CH S 1-515 OCH(CH₃)CH₃ H Cl CH S 1-516 OCH(CH₃)CH₃ Cl H CH S 1-517 OCH(CH₃)CH₃ H NO₂ CH S

TABLE 22 Compound R² R³ R⁴ A Y 1-518 OCH(CH₃)CH₃ NO₂ H CH S 1-519 OCH₂CH═CH₂ H H CH S 1-520 OCH₂CH═CH₂ H Cl CH S 1-521 OCH₂CH═CH₂ Cl H CH S 1-522 OCH₂CH═CH₂ H NO₂ CH S 1-523 OCH₂CH═CH₂ NO₂ H CH S 1-524 OCH(CH₃)CH═CH₂ H H CH S 1-525 OCH(CH₃)CH═CH₂ H Cl CH S 1-526 OCH(CH₃)CH═CH₂ Cl H CH S 1-527 OCH(CH₃)CH═CH₂ H NO₂ CH S 1-528 OCH(CH₃)CH═CH₂ NO₂ H CH S 1-529 OCH₂C(Cl)═CH₂ H H CH S 1-530 OCH₂C(Cl)═CH₂ H Cl CH S 1-531 OCH₂C(Cl)═CH₂ Cl H CH S 1-532 OCH₂C(Cl)═CH₂ H NO₂ CH S 1-533 OCH₂C(Cl)═CH₂ NO₂ H CH S 1-534 OCH₂C≡CH H H CH S 1-535 OCH₂C≡CH H Cl CH S 1-536 OCH₂C≡CH Cl H CH S 1-537 OCH₂C≡CH H NO₂ CH S 1-538 OCH₂C≡CH NO₂ H CH S 1-539 OCH(CH₃)C≡CH H H CH S 1-540 OCH(CH₃)C≡CH H Cl CH S 1-541 OCH(CH₃)C≡CH Cl H CH S 1-542 OCH(CH₃)C≡CH H NO₂ CH S

TABLE 23 Compound R² R³ R⁴ A Y 1-543 OCH(CH₃)C≡CH NO₂ H CH S 1-544 OCH(CH₃)COOH H H CH S 1-545 OCH(CH₃)COOH H Cl CH S 1-546 OCH(CH₃)COOH Cl H CH S 1-547 OCH(CH₃)COOH H NO₂ CH S 1-548 OCH(CH₃)COOH NO₂ H CH S 1-549 OCH(CH₃)COOMe H H CH S 1-550 OCH(CH₃)COOMe H Cl CH S 1-551 OCH(CH₃)COOMe Cl H CH S 1-552 OCH(CH₃)COOMe H NO₂ CH S 1-553 OCH(CH₃)COOMe NO₂ H CH S 1-554 OCH(CH₃)COOEt H H CH S 1-555 OCH(CH₃)COOEt H Cl CH S 1-556 OCH(CH₃)COOEt Cl H CH S 1-557 OCH(CH₃)COOEt H NO₂ CH S 1-558 OCH(CH₃)COOEt NO₂ H CH S 1-559 OCH(CH₃)COOPr H H CH S 1-560 OCH(CH₃)COOPr H Cl CH S 1-561 OCH(CH₃)COOPr Cl H CH S 1-562 OCH(CH₃)COOPr H NO₂ CH S 1-563 OCH(CH₃)COOPr NO₂ H CH S 1-564 OCH(CH₃)COO-i-Pr H H CH S 1-565 OCH(CH₃)COO-i-Pr H Cl CH S 1-566 OCH(CH₃)COO-i-Pr Cl H CH S 1-567 OCH(CH₃)COO-i-Pr H NO₂ CH S

TABLE 24 Compound R² R³ R⁴ A Y 1-568 OCH(CH₃)COO-i-Pr NO₂ H CH S 1-569 OCH(CH₃)COOBu H H CH S 1-570 OCH(CH₃)COOBu H Cl CH S 1-571 OCH(CH₃)COOBu Cl H CH S 1-572 OCH(CH₃)COOBu H NO₂ CH S 1-573 OCH(CH₃)COOBu NO₂ H CH S 1-574 OCH(CH₃)COOPen H H CH S 1-575 OCH(CH₃)COOPen H Cl CH S 1-576 OCH(CH₃)COOPen Cl H CH S 1-577 DCH(CH₃)COOPen H NO₂ CH S 1-578 OCH(CH₃)COOPen NO₂ H CH S 1-579 OCH(CH₃)COO-c-Pen H H CH S 1-580 OCH(CH₃)COO-c-Pen H Cl CH S 1-581 OCH(CH₃)COO-c-Pen Cl H CH S 1-582 OCH(CH₃)COO-c-Pen H NO₂ CH S 1-583 OCH(CH₃)COO-c-Pen NO₂ H CH S 1-584 OCH(CH₃)COOHex H H CH S 1-585 OCH(CH₃)COOHex H Cl CH S 1-586 OCH(CH₃)COOHex Cl H CH S 1-587 OCH(CH₃)COOHex H NO₂ CH S 1-588 OCH(CH₃)COOHex NO₂ H CH S 1-589 OCH(CH₃)COO-c-Hex H H CH S 1-590 OCH(CH₃)COO-c-Hex H Cl CH S 1-591 OCH(CH₃)COO-c-Hex Cl H CH S 1-592 OCH(CH₃)COO-c-Hex H NO₂ CH S

TABLE 25 Com- pound R² R³ R⁴ A Y 1-593 OCH(CH₃)COO-c-Hex NO₂ H CH S 1-594 OCH(CH₃)CO₂CH₂CO₂H H H CH S 1-595 OCH(CH₃)CO₂CH₂CO₂H H Cl CH S 1-596 OCH(CH₃)CO₂CH₂CO₂H Cl H CH S 1-597 OCH(CH₃)CO₂CH₂CO₂H H NO₂ CH S 1-598 OCH(CH₃)CO₂CH₂CO₂H NO₂ H CH S 1-599 OCH(CH₃)CO₂CH₂CO₂Me H H CH S 1-600 OCH(CH₃)CO₂CH₂CO₂Me H Cl CH S 1-601 OCH(CH₃)CO₂CH₂CO₂Me Cl H CH S 1-602 OCH(CH₃)CO₂CH₂CO₂Me H NO₂ CH S 1-603 OCH(CH₃)CO₂CH₂CO₂Me NO₂ H CH S 1-604 OCH(CH₃)CO₂CH₂CO₂Et H H CH S 1-605 OCH(CH₃)CO₂CH₂CO₂Et H Cl CH S 1-606 OCH(CH₃)CO₂CH₂CO₂Et Cl H CH S 1-607 OCH(CH₃)CO₂CH₂CO₂Et H NO₂ CH S 1-608 OCH(CH₃)CO₂CH₂CO₂Et NO₂ H CH S 1-609 OCH(CH₃)CO₂CH(CH₃)CO₂H H H CH S 1-610 OCH(CH₃)CO₂CH(CH₃)CO₂H H Cl CH S 1-611 OCH(CH₃)CO₂CH(CH₃)CO₂H Cl H CH S 1-612 OCH(CH₃)CO₂CH(CH₃)CO₂H H NO₂ CH S 1-613 OCH(CH₃)CO₂CH(CH₃)CO₂H NO₂ H CH S 1-614 OCH(CH₃)CO₂CH(CH₃)CO₂Me H H CH S 1-615 OCH(CH₃)CO₂CH(CH₃)CO₂Me H Cl CH S 1-616 OCH(CH₃)CO₂CH(CH₃)CO₂Me Cl H CH S 1-617 OCH(CH₃)CO₂CH(CH₃)CO₂Me H NO₂ CH S

TABLE 26 Com- pound R² R³ R⁴ A Y 1-618 OCH(CH₃)CO₂CH(CH₃)CO₂Me NO₂ H CH S 1-619 OCH(CH₃)CO₂CH(CH₃)CO₂Et H H CH S 1-620 OCH(CH₃)CO₂CH(CH₃)CO₂Et H Cl CH S 1-621 OCH(CH₃)CO₂CH(CH₃)CO₂Et Cl H CH S 1-622 OCH(CH₃)CO₂CH(CH₃)CO₂Et H NO₂ CH S 1-623 OCH(CH₃)CO₂CH(CH₃)CO₂Et NO₂ H CH S 1-624 SCH₃ H H CH S 1-625 SCH₃ H Cl CH S 1-626 SCH₃ Cl H CH S 1-627 SCH₃ H NO₂ CH S 1-628 SCH₃ NO₂ H CH S 1-629 SCH(CH₃)CH₃ H H CH S 1-630 SCH(CH₃)CH₃ H Cl CH S 1-631 SCH(CH₃)CH₃ Cl H CH S 1-632 SCH(CH₃)CH₃ H NO₂ CH S 1-633 SCH(CH₃)CH₃ NO₂ H CH S 1-634 SCHCH═CH₂ H H CH S 1-635 SCHCH═CH₂ H Cl CH S 1-636 SCHCH═CH₂ Cl H CH S 1-637 SCHCH═CH₂ H NO₂ CH S 1-638 SCHCH═CH₂ NO₂ H CH S 1-639 SCHC≡CH H H CH S 1-640 SCHC≡CH H Cl CH S 1-641 SCHC≡CH Cl H CH S 1-642 SCHC≡CH H NO₂ CH S

TABLE 27 Compound R² R³ R⁴ A Y 1-643 SCHC≡CH NO₂ H CH S 1-644 SCH₂COOH H H CH S 1-645 SCH₂COOH H Cl CH S 1-646 SCH₂COOH Cl H CH S 1-647 SCH₂COOH H NO₂ CH S 1-648 SCH₂COOH NO₂ H CH S 1-649 SCH₂COOMe H H CH S 1-650 SCH₂COOMe H Cl CH S 1-651 SCH₂COOMe Cl H CH S 1-652 SCH₂COOMe H NO₂ CH S 1-653 SCH₂COOMe NO₂ H CH S 1-654 SCH₂COOEt H H CH S 1-655 SCH₂COOEt H Cl CH S 1-656 SCH₂COOEt Cl H CH S 1-657 SCH₂COOEt H NO₂ CH S 1-658 SCH₂COOEt NO₂ H CH S 1-659 SCH(CH₃)COOH H H CH S 1-660 SCH(CH₃)COOH H Cl CH S 1-661 SCH(CH₃)COOH Cl H CH S 1-662 SCH(CH₃)COOH H NO₂ CH S 1-663 SCH(CH₃)COOH NO₂ H CH S 1-664 SCH(CH₃)COOMe H H CH S 1-665 SCH(CH₃)COOMe H Cl CH S 1-666 SCH(CH₃)COOMe Cl H CH S 1-667 SCH(CH₃)COOMe H NO₂ CH S

TABLE 28 Compound R² R³ R⁴ A Y 1-668 SCH(CH₃)COOMe NO₂ H CH S 1-669 SCH(CH₃)COOEt H H CH S 1-670 SCH(CH₃)COOEt H Cl CH S 1-671 SCH(CH₃)COOEt Cl H CH S 1-672 SCH(CH₃)COOEt H NO₂ CH S 1-673 SCH(CH₃)COOEt NO₂ H CH S 1-674 SCH(CH₃)COO-i-Pr H H CH S 1-675 SCH(CH₃)COO-i-Pr H Cl CH S 1-676 SCH(CH₃)COO-i-Pr Cl H CH S 1-677 SCH(CH₃)COO-i-Pr H NO₂ CH S 1-678 SCH(CH₃)COO-i-Pr NO₂ H CH S 1-679 SCH(CH₃)CO₂CH₂CO₂H H H CH S 1-680 SCH(CH₃)CO₂CH₂CO₂H H Cl CH S 1-681 SCH(CH₃)CO₂CH₂CO₂H Cl H CH S 1-682 SCH(CH₃)CO₂CH₂CO₂H H NO₂ CH S 1-683 SCH(CH₃)CO₂CH₂CO₂H NO₂ H CH S 1-684 SCH(CH₃)CO₂CH₂CO₂Me H H CH S 1-685 SCH(CH₃)CO₂CH₂CO₂Me H Cl CH S 1-686 SCH(CH₃)CO₂CH₂CO₂Me Cl H CH S 1-687 SCH(CH₃)CO₂CH₂CO₂Me H NO₂ CH S 1-688 SCH(CH₃)CO₂CH₂CO₂Me NO₂ H CH S 1-689 SCH(CH₃)CO₂CH₂CO₂Et H H CH S 1-690 SCH(CH₃)CO₂CH₂CO₂Et H Cl CH S 1-691 SCH(CH₃)CO₂CH₂CO₂Et Cl H OH S 1-692 SCH(CH₃)CO₂CH₂CO₂Et H NO₂ CH S

TABLE 29 Com- pound R² R³ R⁴ A Y 1-693 SCH(CH₃)CO₂CH₂CO₂Et NO₂ H CH S 1-694 SCH(CH₃)CO₂CH(CH₃)CO₂H H H CH S 1-695 SCH(CH₃)CO₂CH(CH₃)CO₂H H Cl CH S 1-696 SCH(CH₃)CO₂CH(CH₃)CO₂H Cl H CH S 1-697 SCH(CH₃)CO₂CH(CH₃)CO₂H H NO₂ CH S 1-698 SCH(CH₃)CO₂CH(CH₃)CO₂H NO₂ H CH S 1-699 SCH(CH₃)CO₂CH(CH₃)CO₂Me H H CH S 1-700 SCH(CH₃)CO₂CH(CH₃)CO₂Me H Cl CH S 1-701 SCH(CH₃)CO₂CH(CH₃)CO₂Me Cl H CH S 1-702 SCH(CH₃)CO₂CH(CH₃)CO₂Me H NO₂ CH S 1-703 SCH(CH₃)CO₂CH(CH₃)CO₂Me NO₂ H CH S 1-704 SCH(CH₃)CO₂CH(CH₃)CO₂Et H H CH S 1-705 SCH(CH₃)CO₂CH(CH₃)CO₂Et H Cl CH S 1-706 SCH(CH₃)CO₂CH(CH₃)CO₂Et Cl H CH S 1-707 SCH(CH₃)CO₂CH(CH₃)CO₂Et H NO₂ CH S 1-708 SCH(CH₃)CO₂CH(CH₃)CO₂Et NO₂ H CH S 1-709 H NO₂ H CH S 1-710 C≡N H H CH S 1-711 C≡N H Cl CH S 1-712 C≡N Cl H CH S 1-713 C≡N H NO₂ CH S 1-714 C≡N NO₂ H CH S 1-715 C(═O)H H H CH S 1-716 C(═O)H H Cl CH S 1-717 C(═O)H Cl H CH S

TABLE 30 Compound R² R³ R⁴ A Y 1-718 C(═O)H H NO₂ CH S 1-719 C(═O)H NO₂ H CH S 1-720 C(═O)NH₂ H H CH S 1-721 C(═O)NH₂ H Cl CH S 1-722 C(═O)NH₂ Cl H CH S 1-723 C(═O)NH₂ H NO₂ CH S 1-724 C(═O)NH₂ NO₂ H CH S 1-725 CO₂H H H CH S 1-726 CO₂H H Cl CH S 1-727 CO₂H Cl H CH S 1-728 CO₂H H NO₂ CH S 1-729 CO₂H NO₂ H CH S 1-730 CO₂Me H H CH S 1-731 CO₂Me H Cl CH S 1-732 CO₂Me Cl H CH S 1-733 CO₂Me H NO₂ CH S 1-734 CO₂Me NO₂ H CH S 1-735 CO₂Et H H CH S 1-736 CO₂Et H Cl CH S 1-737 CO₂Et Cl H CH S 1-738 CO₂Et H NO₂ CH S 1-739 CO₂Et NO₂ H CH S 1-740 CO₂CH₂CO₂H H H CH S 1-741 CO₂CH₂CO₂H H Cl CH S 1-742 CO₂CH₂CO₂H Cl H CH S

TABLE 31 Compound R² R³ R⁴ A Y 1-743 CO₂CH₂CO₂H H NO₂ CH S 1-744 CO₂CH₂CO₂H NO₂ H CH S 1-745 CO₂CH₂CO₂Me H H CH S 1-746 CO₂CH₂CO₂Me H Cl CH S 1-747 CO₂CH₂CO₂Me Cl H CH S 1-748 CO₂CH₂CO₂Me H NO₂ CH S 1-749 CO₂CH₂CO₂Me NO₂ H CH S 1-750 CO₂CH₂CO₂Et H H CH S 1-751 CO₂CH₂CO₂Et H Cl CH S 1-752 CO₂CH₂CO₂Et Cl H CH S 1-753 CO₂CH₂CO₂Et H NO₂ CH S 1-754 CO₂CH₂CO₂Et NO₂ H CH S 1-755 CO₂CH(CH₃)CO₂H H H CH S 1-756 CO₂CH(CH₃)CO₂H H Cl CH S 1-757 CO₂CH(CH₃)CO₂H Cl H CH S 1-758 CO₂CH(CH₃)CO₂H H NO₂ CH S 1-759 CO₂CH(CH₃)CO₂H NO₂ H CH S 1-760 CO₂CH(CH₃)CO₂Me H H CH S 1-761 CO₂CH(CH₃)CO₂Me H Cl CH S 1-762 CO₂CH(CH₃)CO₂Me Cl H CH S 1-763 CO₂CH(CH₃)CO₂Me H NO₂ CH S 1-764 CO₂CH(CH₃)CO₂Me NO₂ H CH S 1-765 CO₂CH(CH₃)CO₂Et H H CH S 1-766 CO₂CH(CH₃)CO₂Et H Cl CH S 1-767 CO₂CH(CH₃)CO₂Et Cl H CH S

TABLE 32 Compound R² R³ R⁴ A Y 1-768 CO₂CH(CH₃)CO₂Et H NO₂ CH S 1-769 CO₂CH(CH₃)CO₂Et NO₂ H CH S 1-770 CO₂C(CH₃)₂CO₂H H H CH S 1-771 CO₂C(CH₃)₂CO₂H H Cl CH S 1-772 CO₂C(CH₃)₂CO₂H Cl H CH S 1-773 CO₂C(CH₃)₂CO₂H H NO₂ CH S 1-774 CO₂C(CH₃)₂CO₂H NO₂ H CH S 1-775 CO₂C(CH₃)₂CO₂Me H H CH S 1-776 CO₂C(CH₃)₂CO₂Me H Cl CH S 1-777 CO₂C(CH₃)₂CO₂Me Cl H CH S 1-778 CO₂C(CH₃)₂CO₂Me H NO₂ CH S 1-779 CO₂C(CH₃)₂CO₂Me NO₂ H CH S 1-780 CO₂C(CH₃)₂CO₂Et H H CH S 1-781 CO₂C(CH₃)₂CO₂Et H Cl CH S 1-782 CO₂C(CH₃)₂CO₂Et Cl H CH S 1-783 CO₂C(CH₃)₂CO₂Et H NO₂ CH S 1-784 CO₂C(CH₃)₂CO₂Et NO₂ H CH S 1-785 CH₃ H H CH S 1-786 CH₃ H Cl CH S 1-787 CH₃ Cl H CH S 1-788 CH₃ H NO₂ CH S 1-789 CH₃ NO₂ H CH S 1-790 CF₃ H H CH S 1-791 CF₃ H Cl CH S 1-792 CF₃ Cl H CH S

TABLE 33 Compound R² R³ R⁴ A Y 1-793 CF₃ H NO₂ CH S 1-794 CF₃ NO₂ H CH S 1-795 CH═CHCO₂H H H CH S 1-796 CH═CHCO₂H H Cl CH S 1-797 CH═CHCO₂H Cl H CH S 1-798 CH═CHCO₂H H NO₂ CH S 1-799 CH═CHCO₂H NO₂ H CH S 1-800 CH═CHCO₂Me H H CH S 1-801 CH═CHCO₂Me H Cl CH S 1-802 CH═CHCO₂Me Cl H CH S 1-803 CH═CHCO₂Me H NO₂ CH S 1-804 CH═CHCO₂Me NO₂ H CH S 1-805 CH═CHCO₂Et H H CH S 1-806 CH═CHCO₂Et H Cl CH S 1-807 CH═CHCO₂Et Cl H CH S 1-808 CH═CHCO₂Et H NO₂ CH S 1-809 CH═CHCO₂Et NO₂ H CH S 1-810 CH₂CH₂CO₂H H H CH S 1-811 CH₂CH₂CO₂H H Cl CH S 1-812 CH₂CH₂CO₂H Cl H CH S 1-813 CH₂CH₂CO₂H H NO₂ CH S 1-814 CH₂CH₂CO₂H NO₂ H CH S 1-815 CH₂CH₂CO₂Me H H CH S 1-816 CH₂CH₂CO₂Me H Cl CH S 1-817 CH₂CH₂CO₂Me Cl H CH S

TABLE 34 Compound R² R³ R⁴ A Y 1-818 CH₂CH₂CO₂Me H NO₂ CH S 1-819 CH₂CH₂CO₂Me NO₂ H CH S 1-820 CH₂CH₂CO₂Et H H CH S 1-821 CH₂CH₂CO₂Et H Cl CH S 1-822 CH₂CH₂CO₂Et Cl H CH S 1-823 CH₂CH₂CO₂Et H NO₂ CH S 1-824 CH₂CH₂CO₂Et NO₂ H CH S 1-825 CH₂CH(Cl)CO₂H H H CH S 1-826 CH₂CH(Cl)CO₂H H Cl CH S 1-827 CH₂CH(Cl)CO₂H Cl H CH S 1-828 CH₂CH(Cl)CO₂H H NO₂ CH S 1-829 CH₂CH(Cl)CO₂H NO₂ H CH S 1-830 CH₂CH(Cl)CO₂Me H H CH S 1-831 CH₂CH(Cl)CO₂Me H Cl CH S 1-832 CH₂CH(Cl)CO₂Me Cl H CH S 1-833 CH₂CH(Cl)CO₂Me H NO₂ CH S 1-834 CH₂CH(Cl)CO₂Me NO₂ H CH S 1-835 CH₂CH(Cl)CO₂Et H H CH S 1-836 CH₂CH(Cl)CO₂Et H Cl CH S 1-837 CH₂CH(Cl)CO₂Et Cl H CH S 1-838 CH₂CH(Cl)CO₂Et H NO₂ CH S 1-839 CH₂CH(Cl)CO₂Et NO₂ H CH S 1-840 C(═O)CH₃ H H CH S 1-841 C(═O)CH₃ H Cl CH S 1-842 C(═O)CH₃ Cl H CH S

TABLE 35 Compound R² R³ R⁴ A Y 1-843 C(═O)CH₃ H NO₂ CH S 1-844 C(═O)CH₃ NO₂ H CH S 1-845 C(CH₃)═NOH H H CH S 1-846 C(CH₃)═NOH H Cl CH S 1-847 C(CH₃)═NOH Cl H CH S 1-848 C(CH₃)═NOH H NO₂ CH S 1-849 C(CH₃)═NOH NO₂ H CH S 1-850 C(CH₃)═NOMe H H CH S 1-851 C(CH₃)═NOMe H Cl CH S 1-852 C(CH₃)═NOMe Cl H CH S 1-853 C(CH₃)═NOMe H NO₂ CH S 1-854 C(CH₃)═NOMe NO₂ H CH S 1-855 F H H CH S 1-856 F H Cl CH S 1-857 F Cl H CH S 1-858 F H NO₂ CH S 1-859 F NO₂ H CH S 1-860 H H Cl CH O 1-861 H Cl H CH O 1-862 H Cl Cl CH O 1-863 H H Cl CH S 1-864 H Cl H CH S 1-865 H Cl Cl CH S 1-866 CH═NOH H Cl CH O 1-867 CH═NOH Cl H CH O

TABLE 36 Compound R² R³ R⁴ A Y 1-868 CH═NOH H NO₂ CH O 1-869 CH═NOH NO₂ H CH O 1-870 CH═NOCH₃ H H CH O 1-871 CH═NOCH₃ H Cl CH O 1-872 CH═NOCH₃ Cl H CH O 1-873 CH═NOCH₃ H NO₂ CH O 1-874 CH═NOCH₃ NO₂ H CH O 1-875 H H H N O 1-876 H H Cl N O 1-877 H Cl H N O 1-878 H H NO₂ N O 1-879 H NO₂ H N O 1-880 OH H H N O 1-881 OH H Cl N O 1-882 OH Cl H N O 1-883 OH H NO₂ N O 1-884 OH NO₂ H N O 1-885 OCH₃ H H N O 1-886 OCH₃ H Cl N O 1-887 OCH₃ Cl H N O 1-888 OCH₃ H NO₂ N O 1-889 OCH₃ NO₂ H N O 1-890 OCH(CH₃)CH₃ H H N O 1-891 OCH(CH₃)CH₃ H Cl N O 1-892 OCH(CH₃)CH₃ Cl H N O

TABLE 37 Compound R² R³ R⁴ A Y 1-893 OCH(CH₃)CH₃ H NO₂ N O 1-894 OCH(CH₃)CH₃ NO₂ H N O 1-895 OCH₂C≡CH H H N O 1-896 OCH₂C≡CH H Cl N O 1-897 OCH₂C≡CH Cl H N O 1-898 OCH₂C≡CH H NO₂ N O 1-899 OCH₂C≡CH NO₂ H N O 1-900 OCH(CH₃)C≡CH H H N O 1-901 OCH(CH₃)C≡CH H Cl N O 1-902 OCH(CH₃)C≡CH Cl H N O 1-903 OCH(CH₃)C≡CH H NO₂ N O 1-904 OCH(CH₃)C≡CH NO₂ H N O 1-905 OCH₂CH═CH₂ H H N O 1-906 OCH₂CH═CH₂ H Cl N O 1-907 OCH₂CH═CH₂ Cl H N O 1-908 OCH₂CH═CH₂ H NO₂ N O 1-909 OCH₂CH═CH₂ NO₂ H N O 1-910 OCH₂CO₂H H H N O 1-911 OCH₂CO₂H H Cl N O 1-912 OCH₂CO₂H Cl H N O 1-913 OCH₂CO₂H H NO₂ N O 1-914 OCH₂CO₂H NO₂ H N O 1-915 OCH₂CO₂Et H H N O 1-916 OCH₂CO₂Et H Cl N O 1-917 OCH₂CO₂Et Cl H N O

TABLE 38 Compound R² R³ R⁴ A Y 1-918 OCH₂CO₂Et H NO₂ N O 1-919 OCH₂CO₂Et NO₂ H N O 1-920 OCH(CH₃)CO₂H H H N O 1-921 OCH(CH₃)CO₂H H Cl N O 1-922 OCH(CH₃)CO₂H Cl H N O 1-923 OCH(CH₃)CO₂H H NO₂ N O 1-924 OCH(CH₃)CO₂H NO₂ H N O 1-925 OCH(CH₃)CO₂Me H H N O 1-926 OCH(CH₃)CO₂Me H Cl N O 1-927 OCH(CH₃)CO₂Me Cl H N O 1-928 OCH(CH₃)CO₂Me H NO₂ N O 1-929 OCH(CH₃)CO₂Me NO₂ H N O 1-930 OCH(CH₃)CO₂Et H H N O 1-931 OCH(CH₃)CO₂Et H Cl N O 1-932 OCH(CH₃)CO₂Et Cl H N O 1-933 OCH(CH₃)CO₂Et H NO₂ N O 1-934 OCH(CH₃)CO₂Et NO₂ H N O 1-935 CO₂H H H N O 1-936 CO₂H H Cl N O 1-937 CO₂H Cl H N O 1-938 CO₂H H NO₂ N O 1-939 CO₂H NO₂ H N O 1-940 CO₂Me H H N O 1-941 CO₂Me H Cl N O 1-942 CO₂Me Cl H N O

TABLE 39 Compound R² R³ R⁴ A Y 1-943 CO₂Me H NO₂ N O 1-944 CO₂Me NO₂ H N O 1-945 CO₂Et H H N O 1-946 CO₂Et H Cl N O 1-947 CO₂Et Cl H N O 1-948 CO₂Et H NO₂ N O 1-949 CO₂Et NO₂ H N O 1-950 CO₂CH(CH₃)CO₂Et H H N O 1-951 CO₂CH(CH₃)CO₂Et H Cl N O 1-952 CO₂CH(CH₃)CO₂Et Cl H N O 1-953 CO₂CH(CH₃)CO₂Et H NO₂ N O 1-954 CO₂CH(CH₃)CO₂Et NO₂ H N O 1-955 CO₂C(CH₃)₂CO₂Et H H N O 1-956 CO₂C(CH₃)₂CO₂Et H Cl N O 1-957 CO₂C(CH₃)₂CO₂Et Cl H N O 1-958 CO₂C(CH₃)₂CO₂Et H NO₂ N O 1-959 CO₂C(CH₃)₂CO₂Et NO₂ H N O 1-960 C(═O)H H H N O 1-961 C(═O)H H Cl N O 1-962 C(═O)H Cl H N O 1-963 C(═O)H H NO₂ N O 1-964 C(═O)H NO₂ H N O 1-965 CH═CHCO₂Et H H N O 1-966 CH═CHCO₂Et H Cl N O 1-967 CH═CHCO₂Et Cl H N O

TABLE 40 Compound R² R³ R⁴ A Y 1-968 CH═CHCO₂Et H NO₂ N O 1-969 CH═CHCO₂Et NO₂ H N O 1-970 CH═NOH H H N O 1-971 CH═NOH H Cl N O 1-972 CH═NOH Cl H N O 1-973 CH═NOH H NO₂ N O 1-974 CH═NOH NO₂ H N O 1-975 CH═NOCH₃ H H N O 1-976 CH═NOCH₃ H Cl N O 1-977 CH═NOCH₃ Cl H N O 1-978 CH═NOCH₃ H NO₂ N O 1-979 CH═NOCH₃ NO₂ H N O 1-980 CH₂CH₂CO₂Et H H N O 1-981 CH₂CH₂CO₂Et H Cl N O 1-982 CH₂CH₂CO₂Et Cl H N O 1-983 CH₂CH₂CO₂Et H NO₂ N O 1-984 CH₂CH₂CO₂Et NO₂ H N O 1-985 CH₂CH(Cl)CO₂Et H H N O 1-986 CH₂CH(Cl)CO₂Et H Cl N O 1-987 CH₂CH(Cl)CO₂Et Cl H N O 1-988 CH₂CH(Cl)CO₂Et H NO₂ N O 1-989 CH₂CH(Cl)CO₂Et NO₂ H N O 1-990 H Cl Cl N O 1-991 CF₃ H Cl N O 1-992 CF₃ Cl H N O

TABLE 41 Compound R² R³ R⁴ A Y 1-2001 H H H CH CH 1-2002 Cl H H CH CH 1-2003 H Cl H CH CH 1-2004 H H Cl CH CH 1-2005 NO₂ H H CH CH 1-2006 H NO₂ H CH CH 1-2007 H H NO₂ CH CH 1-2008 OH H H CH CH 1-2009 OCH₃ H H CH CH 1-2010 OCH₂CO₂CH₃ H H CH CH 1-2011 OCH₂CO₂C₂H₅ H H CH CH 1-2012 OCH(CH₃)CO₂CH₃ H H CH CH 1-2013 OCH(CH₃)CO₂C₂H₅ H H CH CH 1-2014 OC(CH₃)₂CO₂CH₃ H H CH CH 1-2015 OC(CH₃)₂CO₂C₂H₅ H H CH CH 1-2016 CO₂H H H CH CH 1-2017 CO₂CH₃ H H CH CH 1-2018 CO₂C₂H₅ H H CH CH 1-2019 CO₂CH₂CO₂C₂H₅ H H CH CH 1-2020 CO₂CH(CH₃)CO₂C₂H₅ H H CH CH 1-2021 CO₂C(CH₃)₂CO₂C₂H₅ H H CH CH 1-2022 OH Cl H CH CH 1-2023 OCH₃ Cl H CH CH 1-2024 OCH₂CO₂CH₃ Cl H CH CH 1-2025 OCH₂CO₂C₂H₅ Cl H CH CH

TABLE 42 Compound R² R³ R⁴ A Y 1-2026 OCH(CH₃)CO₂CH₃ Cl H CH CH 1-2027 OCH(CH₃)CO₂C₂H₅ Cl H CH CH 1-2028 OC(CH₃)₂CO₂CH₃ Cl H CH CH 1-2029 OC(CH₃)₂CO₂C₂H₅ Cl H CH CH 1-2030 CO₂H Cl H CH CH 1-2031 CO₂CH₃ Cl H CH CH 1-2032 CO₂C₂H₅ Cl H CH CH 1-2033 CO₂CH₂CO₂C₂H₅ Cl H CH CH 1-2034 CO₂CH(CH₃)CO₂C₂H₅ Cl H CH CH 1-2035 CO₂C(CH₃)₂CO₂C₂H₅ Cl H CH CH 1-2036 OH NO₂ H CH CH 1-2037 OCH₃ NO₂ H CH CH 1-2038 OCH₂CO₂CH₃ NO₂ H CH CH 1-2039 OCH₂CO₂C₂H₅ NO₂ H CH CH 1-2040 OCH(CH₃)CO₂CH₃ NO₂ H CH CH 1-2041 OCH(CH₃)CO₂C₂H₅ NO₂ H CH CH 1-2042 OC(CH₃)₂CO₂CH₃ NO₂ H CH CH 1-2043 OC(CH₃)₂CO₂C₂H₅ NO₂ H CH CH 1-2044 CO₂H NO₂ H CH CH 1-2045 CO₂CH₃ NO₂ H CH CH 1-2046 CO₂C₂H₅ NO₂ H CH CH 1-2047 CO₂CH₂CO₂C₂H₅ NO₂ H CH CH 1-2048 CO₂CH(CH₃)CO₂C₂H₅ NO₂ H CH CH 1-2049 CO₂C(CH₃)₂CO₂C₂H₅ NO₂ H CH CH 1-2050 Cl H Cl CH CH

TABLE 43 Compound R² R³ R⁴ A Y 1-2051 H H H N CH 1-2052 Cl H H N CH 1-2053 H Cl H N CH 1-2054 H H Cl N CH 1-2055 NO₂ H H N CH 1-2056 H NO₂ H N CH 1-2057 H H NO₂ N CH 1-2058 OH H H N CH 1-2059 OCH₃ H H N CH 1-2060 OCH₂CO₂CH₃ H H N CH 1-2061 OCH₂CO₂C₂H₅ H H N CH 1-2062 OCH(CH₃)CO₂CH₃ H H N CH 1-2063 OCH(CH₃)₂CO₂C₂H₅ H H N CH 1-2064 OC(CH₃)₂CO₂CH₃ H H N CH 1-2065 OC(CH₃)₂CO₂C₂H₅ H H N CH 1-2066 CO₂H H H N CH 1-2067 CO₂CH₃ H H N CH 1-2068 CO₂C₂H₅ H H N CH 1-2069 CO₂CH₂CO₂C₂H₅ H H N CH 1-2070 CO₂CH(CH₃)CO₂C₂H₅ H H N CH 1-2071 CO₂C(CH₃)₂CO₂C₂H₅ H H N CH 1-2072 OH Cl H N CH 1-2073 OCH₃ Cl H N CH 1-2074 OCH₂CO₂CH₃ Cl H N CH 1-2075 OCH₂CO₂C₂H₅ Cl H N CH

TABLE 44 Compound R² R³ R⁴ A Y 1-2076 OCH(CH₃)CO₂CH₃ Cl H N CH 1-2077 OCH(CH₃)CO₂C₂H₅ Cl H N CH 1-2078 OC(CH₃)₂CO₂CH₃ Cl H N CH 1-2079 OC(CH₃)₂CO₂C₂H₅ Cl H N CH 1-2080 CO₂H Cl H N CH 1-2081 CO₂CH₃ Cl H N CH 1-2082 CO₂C₂H₅ Cl H N CH 1-2083 CO₂CH₂CO₂C₂H₅ Cl H N CH 1-2084 CO₂CH(CH₃)CO₂C₂H₅ Cl H N CH 1-2085 CO₂C(CH₃)₂CO₂C₂H₅ Cl H N CH 1-2086 OH NO₂ H N CH 1-2087 OCH₃ NO₂ H N CH 1-2088 OCH₂CO₂CH₃ NO₂ H N CH 1-2089 OCH₂CO₂C₂H₅ NO₂ H N CH 1-2090 OCH(CH₃)CO₂CH₃ NO₂ H N CH 1-2091 OCH(CH₃)CO₂C₂H₅ NO₂ H N CH 1-2092 OC(CH₃)₂CO₂CH₃ NO₂ H N CH 1-2093 OC(CH₃)₂CO₂C₂H₅ NO₂ H N CH 1-2094 CO₂H NO₂ H N CH 1-2095 CO₂CH₃ NO₂ H N CH 1-2096 CO₂C₂H₅ NO₂ H N CH 1-2097 CO₂CH₂CO₂C₂H₅ NO₂ H N CH 1-2098 CO₂CH(CH₃)CO₂C₂H₅ NO₂ H N CH 1-2099 CO₂C(CH₃)₂CO₂C₂H₅ NO₂ H N CH 1-2100 Cl H Cl N CH

TABLE 45 Compound R² R³ R⁴ A Y 1-2101 H H H CH N 1-2102 Cl H H CH N 1-2103 H Cl H CH N 1-2104 H H Cl CH N 1-2105 NO₂ H H CH N 1-2106 H NO₂ H CH N 1-2107 H H NO₂ CH N 1-2108 OH H H CH N 1-2109 OCH₃ H H CH N 1-2110 OCH₂CO₂CH₃ H H CH N 1-2111 OCH₂CO₂C₂H₅ H H CH N 1-2112 OCH(CH₃)CO₂CH₃ H H CH N 1-2113 OCH(CH₃)CO₂C₂H₅ H H CH N 1-2114 OC(CH₃)₂CO₂CH₃ H H CH N 1-2115 OC(CH₃)₂CO₂C₂H₅ H H CH N 1-2116 CO₂H H H CH N 1-2117 CO₂CH₃ H H CH N 1-2118 CO₂C₂H₅ H H CH N 1-2119 CO₂CH₂CO₂C₂H₅ H H CH N 1-2120 CO₂CH(CH₃)CO₂C₂H₅ H H CH N 1-2121 CO₂C(CH₃)₂CO₂C₂H₅ H H CH N 1-2122 OH Cl H CH N 1-2123 OCH₃ Cl H CH N 1-2124 OCH₂CO₂CH₃ Cl H CH N 1-2125 OCH₂CO₂C₂H₅ Cl H CH N

TABLE 46 Compound R² R³ R⁴ A Y 1-2126 OCH(CH₃)CO₂CH₃ Cl H CH N 1-2127 OCH(CH₃)CO₂C₂H₅ Cl H CH N 1-2128 OC(CH₃)₂CO₂CH₃ Cl H CH N 1-2129 OC(CH₃)₂CO₂C₂H₅ Cl H CH N 1-2130 CO₂H Cl H CH N 1-2131 CO₂CH₃ Cl H CH N 1-2132 CO₂C₂H₅ Cl H CH N 1-2133 CO₂CH₂CO₂C₂H₅ Cl H CH N 1-2134 CO₂CH(CH₃)CO₂C₂H₅ Cl H CH N 1-2135 CO₂C(CH₃)₂CO₂C₂H₅ Cl H CH N 1-2136 OH NO₂ H CH N 1-2137 OCH₃ NO₂ H CH N 1-2138 OCH₂CO₂CH₃ NO₂ H CH N 1-2139 OCH₂CO₂C₂H₅ NO₂ H CH N 1-2140 OCH(CH₃)CO₂CH₃ NO₂ H CH N 1-2141 OCH(CH₃)CO₂C₂H₅ NO₂ H CH N 1-2142 OC(CH₃)₂CO₂CH₃ NO₂ H CH N 1-2143 OC(CH₃)₂CO₂C₂H₅ NO₂ H CH N 1-2144 CO₂H NO₂ H CH N 1-2145 CO₂CH₃ NO₂ H CH N 1-2146 CO₂C₂H₅ NO₂ H CH N 1-2147 CO₂CH₂CO₂C₂H₅ NO₂ H CH N 1-2148 CO₂CH(CH₃)CO₂C₂H₅ NO₂ H CH N 1-2149 CO₂C(CH₃)₂CO₂C₂H₅ NO₂ H CH N 1-2150 Cl H Cl CH N

TABLE 47 Compound R² R³ R⁴ A Y 1-2151 H H H N N 1-2152 Cl H H N N 1-2153 H Cl H N N 1-2154 H H Cl N N 1-2155 NO₂ H H N N 1-2156 H NO₂ H N N 1-2157 H H NO₂ N N 1-2158 OH H H N N 1-2159 OCH₃ H H N N 1-2160 OCH₂CO₂CH₃ H H N N 1-2161 OCH₂CO₂C₂H₅ H H N N 1-2162 OCH(CH₃)CO₂CH₃ H H N N 1-2163 OCH(CH₃)CO₂C₂H₅ H H N N 1-2164 OC(CH₃)₂CO₂CH₃ H H N N 1-2165 OC(CH₃)₂CO₂C₂H₅ H H N N 1-2166 CO₂H H H N N 1-2167 CO₂CH₃ H H N N 1-2168 CO₂C₂H₅ H H N N 1-2169 CO₂CH₂CO₂C₂H₅ H H N N 1-2170 CO₂CH(CH₃)CO₂C₂H₅ H H N N 1-2171 CO₂C(CH₃)₂CO₂C₂H₅ H H N N 1-2172 OH Cl H N N 1-2173 OCH₃ Cl H N N 1-2174 OCH₂CO₂CH₃ Cl H N N 1-2175 OCH₂CO₂C₂H₅ Cl H N N

TABLE 48 Compound R² R³ R⁴ A Y 1-2176 OCH(CH₃)CO₂CH₃ Cl H N N 1-2177 OCH(CH₃)CO₂C₂H₅ Cl H N N 1-2178 OC(CH₃)₂CO₂CH₃ Cl H N N 1-2179 OC(CH₃)₂CO₂C₂H₅ Cl H N N 1-2180 CO₂H Cl H N N 1-2181 CO₂CH₃ Cl H N N 1-2182 CO₂C₂H₅ Cl H N N 1-2183 CO₂CH₂CO₂C₂H₅ Cl H N N 1-2184 CO₂CH(CH₃)CO₂C₂H₅ Cl H N N 1-2185 CO₂C(CH₃)₂CO₂C₂H₅ Cl H N N 1-2186 OH NO₂ H N N 1-2187 OCH₃ NO₂ H N N 1-2188 OCH₂CO₂CH₃ NO₂ H N N 1-2189 OCH₂CO₂C₂H₅ NO₂ H N N 1-2190 OCH(CH₃)CO₂CH₃ NO₂ H N N 1-2191 OCH(CH₃)CO₂C₂H₅ NO₂ H N N 1-2192 OC(CH₃)₂CO₂CH₃ NO₂ H N N 1-2193 OC(CH₃)₂CO₂C₂H₅ NO₂ H N N 1-2194 CO₂H NO₂ H N N 1-2195 CO₂CH₃ NO₂ H N N 1-2196 CO₂C₂H₅ NO₂ H N N 1-2197 CO₂CH₂CO₂C₂H₅ NO₂ H N N 1-2198 CO₂CH(CH₃)CO₂C₂H₅ NO₂ H N N 1-2199 CO₂C(CH₃)₂CO₂C₂H₅ NO₂ H N N 1-2200 Cl H Cl N N

TABLE 49 Compound R² R³ R⁴ A Y 2-1 H H H CH O 2-2 Cl H Cl CH O 2-3 H H H CH S 2-4 H H H N O 2-5 Cl H Cl N O 2-6 H H H N S 2-7 OCH₃ H H CH O 2-8 OCH₃ H H N O 2-9 NHCH₃ H H CH O 2-10 NHCH₃ H H N O 2-11 OCH₂CH═CH₂ H H CH O 2-12 OCH₂CH═CH₂ H H N O 2-13 CO₂CH₂CO₂Et H H CH O 2-14 CO₂CH₂CO₂Et H H N O 2-15 OCH₂CO₂C₂H₅ H H CH O 2-16 OCH₂CO₂C₂H₅ H H N O 2-17 OCH(CH₃)CH═CH₂ H H CH O 2-18 OCH(CH₃)CH═CH₂ H H N O 2-19 CO₂CH(CH₃)CO₂Et H H CH O 2-20 CO₂CH(CH₃)CO₂Et H H N O 2-21 OCH(CH₃)CO₂C₂H₅ H H CH O 2-22 OCH(CH₃)CO₂C₂H₅ H H N O 2-23 OCH(CH₃)C≡CH H H CH O 2-24 OCH(CH₃)C≡CH H H N O 2-25 OCH₂C≡CH H H CH O

TABLE 50 Compound R² R³ R⁴ A Y 2-26 OCH₂C≡CH H H N O 2-27 OCH₃ NO₂ H CH O 2-28 OCH₃ NO₂ H N O 2-29 OCH₃ H Cl CH O 2-30 OCH₃ H Cl N O 2-31 CH₂CO₂CH₃ H H CH O 2-32 CH₂CO₂CH₃ H H N O 2-33 CH₂CO₂CH₃ NO₂ H CH O 2-34 CH₂CO₂CH₃ NO₂ H N O 2-35 CH₂CO₂CH₃ H Cl CH O 2-36 CH₂CO₂CH₃ H Cl N O 2-37 OCH(CH₃)CO₂C₂H₅ NO₂ H CH O 2-38 OCH(CH₃)CO₂C₂H₅ NO₂ H N O 2-39 OCH(CH₃)CO₂C₂H₅ H Cl CH O 2-40 OCH(CH₃)CO₂C₂H₅ H Cl N O 2-41 OCH₂C≡CH NO₂ H CH O 2-42 OCH₂C≡CH NO₂ H N O 2-43 OCH₂C≡CH H Cl CH O 2-44 OCH₂C≡CH H Cl N O 2-45 OCH(CH₃)C≡CH NO₂ H N O 2-46 OCH(CH₃)C≡CH NO₂ H CH O 2-47 OCH(CH₃)C≡CH H Cl N O 2-48 OCH(CH₃)C≡CH H Cl CH O 2-49 SCH(CH₃)CO₂C₂H₅ NO₂ H CH O 2-50 SCH(CH₃)CO₂C₂H₅ NO₂ H N O

TABLE 51 Compound R² R³ R⁴ A Y 2-2001 H H H CH CH 2-2002 H H H CH N 2-2003 H H H N CH 2-2004 H H H N N 2-2005 OCH₃ H H CH CH 2-2006 OCH₃ H H CH N 2-2007 OCH₃ H H N CH 2-2008 OCH₃ H H N N 2-2009 CO₂Et H H CH CH 2-2010 CO₂Et H H CH N 2-2011 CO₂Et H H N CH 2-2012 CO₂Et H H N N 2-2013 OCH₂CO₂C₂H₅ H H CH CH 2-2014 OCH₂CO₂C₂H₅ H H CH N 2-2015 OCH₂CO₂C₂H₅ H H N CH 2-2016 OCH₂CO₂C₂H₅ H H N N 2-2017 OCH(CH₃)CO₂C₂H₅ H H CH CH 2-2018 OCH(CH₃)CO₂C₂H₅ H H CH N 2-2019 OCH(CH₃)CO₂C₂H₅ H H N CH 2-2020 OCH(CH₃)CO₂C₂H₅ H H N N 2-2021 OCH₂C≡CH H H CH CH 2-2022 OCH₂C≡CH H H CH N 2-2023 OCH₂C≡CH H H N CH 2-2024 OCH₂C≡CH H H N N 2-2025 OCH(CH₃)C≡CH H H N N

TABLE 52 Compound R² R³ R⁴ A Y 3-1 H H H CH O 3-2 Cl H Cl CH O 3-3 H H H CH S 3-4 H H H N O 3-5 Cl H Cl N O 3-6 H H H N S 3-7 OCH₃ H H CH O 3-8 OCH₃ H H N O 3-9 NHCH₃ H H CH O 3-10 NHCH₃ H H N O 3-11 OCH₂CH═CH₂ H H CH O 3-12 OCH₂CH═CH₂ H H N O 3-13 CO₂CH₂CO₂Et H H CH O 3-14 CO₂CH₂CO₂Et H H N O 3-15 OCH₂CO₂C₂H₅ H H CH O 3-16 OCH₂CO₂C₂H₅ H H N O 3-17 OCH(CH₃)CH═CH₂ H H CH O 3-18 OCH(CH₃)CH═CH₂ H H N O 3-19 CO₂CH(CH₃)CO₂Et H H CH O 3-20 CO₂CH(CH₃)CO₂Et H H N O 3-21 OCH(CH₃)CO₂C₂H₅ H H CH O 3-22 OCH(CH₃)CO₂C₂H₅ H H N O 3-23 OCH(CH₃)C≡CH H H CH O 3-24 OCH(CH₃)C≡CH H H N O 3-25 OCH₂C≡CH H H CH O

TABLE 53 Compound R² R³ R⁴ A Y 3-26 OCH₂C≡CH H H N O 3-27 OCH₃ NO₂ H CH O 3-28 OCH₃ NO₂ H N O 3-29 OCH₃ H Cl CH O 3-30 OCH₃ H Cl N O 3-31 CH₂CO₂CH₃ H H CH O 3-32 CH₂CO₂CH₃ H H N O 3-33 CH₂CO₂CH₃ NO₂ H CH O 3-34 CH₂CO₂CH₃ NO₂ H N O 3-35 CH₂CO₂CH₃ H Cl CH O 3-36 CH₂CO₂CH₃ H Cl N O 3-37 OCH(CH₃)CO₂C₂H₅ NO₂ H CH O 3-38 OCH(CH₃)CO₂C₂H₅ NO₂ H N O 3-39 OCH(CH₃)CO₂C₂H₅ H Cl CH O 3-40 OCH(CH₃)CO₂C₂H₅ H Cl N O 3-41 OCH₂C≡CH NO₂ H CH O 3-42 OCH₂C≡CH NO₂ H N O 3-43 OCH₂C≡CH H Cl CH O 3-44 OCH₂C≡CH H Cl N O 3-45 OCH(CH₃)C≡CH NO₂ H N O 3-46 OCH(CH₃)C≡CH NO₂ H CH O 3-47 OCH(CH₃)C≡CH H Cl N O 3-48 OCH(CH₃)C≡CH H Cl CH O 3-49 SCH(CH₃)CO₂C₂H₅ NO₂ H CH O 3-50 SCH(CH₃)CO₂C₂H₅ NO₂ H N O

TABLE 54 Compound R² R³ R⁴ A Y 3-2001 H H H CH CH 3-2002 H H H CH N 3-2003 H H H N CH 3-2004 H H H N N 3-2005 OCH₃ H H CH CH 3-2006 OCH₃ H H CH N 3-2007 OCH₃ H H N CH 3-2008 OCH₃ H H N N 3-2009 CO₂Et H H CH CH 3-2010 CO₂Et H H CH N 3-2011 CO₂Et H H N CH 3-2012 CO₂Et H H N N 3-2013 OCH₂CO₂C₂H₅ H H CH CH 3-2014 OCH₂CO₂C₂H₅ H H CH N 3-2015 OCH₂CO₂C₂H₅ H H N CH 3-2016 OCH₂CO₂C₂H₅ H H N N 3-2017 OCH(CH₃)CO₂C₂H₅ H H CH CH 3-2018 OCH(CH₃)CO₂C₂H₅ H H CH N 3-2019 OCH(CH₃)CO₂C₂H₅ H H N CH 3-2020 OCH(CH₃)CO₂C₂H₅ H H N N 3-2021 OCH₂C≡CH H H CH CH 3-2022 OCH₂C≡CH H H CH N 3-2023 OCH₂C≡CH H H N CH 3-2024 OCH₂C≡CH H H N N 3-2025 OCH(CH₃)C≡CH H H N N

For some of the present compounds, melting points or ¹H-NMR data as their physical properties are shown below.

The Present Compound 1-4

m.p.: 132.1° C.

The Present Compound 1-11

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.20 (3H, t, J=7.14 Hz), 1.44 (3H, d, J=6.92 Hz), 3.56 (3H, m), 4.06-4.20 (4H, m), 6.38 (1H, s), 6.42 (1H, d, J=2.33 Hz), 6.67 (1H, dd, J=8.87 Hz, 2.33 Hz), 7.32 (1H, d, J=8.87 Hz), 7.72 (1H, s).

The Present Compound 1-76

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.60 (3H, s), 6.40 (1H, s), 7.39 (1H, d, J=1.52 Hz), 7.51 (1H, d, J=1.52 Hz), 7.91 (1H, s).

The Present Compound 1-77

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.59 (3H, s), 6.40 (1H, s), 7.61 (1H, s), 7.69 (1H, s), 7.84 (1H, s).

The Present Compound 1-80

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 3.58-3.60 (3H, m), 5.47 (1H, s), 6.40 (1H, s), 6.92 (1H, s), 7.56 (1H, s), 7.80 (1H, s).

The Present Compound 1-82

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.60-3.61 (3H, m), 6.41 (1H, s), 7.02 (1H, s), 8.05 (1H, s), 8.35 (1H, s), 10.46 (1H, s).

The Present Compound 1-83

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.59 (3H, s), 3.80 (3H, s), 6.39 (1H, s), 6.64 (1H, d, J=2.19 Hz), 7.00 (1H, d, J=2.19 Hz), 7.85 (1H, s).

The Present Compound 1-84

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 3.60-3.61 (3H, m), 3.91 (3H, s), 6.41 (1H, s), 6.75 (1H, s), 7.61 (1H, s), 7.80 (1H, s).

The Present Compound 1-86

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.61 (3H, m), 3.95 (3H, s), 6.42 (1H, s), 6.89 (1H, s), 8.00 (1H, s), 8.09 (1H, s).

The Present Compound 1-128

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.22 (3H, t, J=7.08 Hz), 1.60 (3H, d, J=6.76 Hz), 3.58 (3H, m), 4.15-4.24 (2H, m), 4.71 (1H, q, J=6.78 Hz), 6.39 (1H, s), 6.66 (1H, d, J=2.33 Hz), 7.03 (1H, d, J=2.33 Hz), 7.86 (1H, s).

The Present Compound 1-129

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.20 (3H, t, J=7.17 Hz), 1.66 (3H, d, J=6.76 Hz), 3.57 (3H, s), 4.18 (2H, q, J=7.10 Hz), 4.72 (1H, q, J=6.85 Hz), 6.38 (1H, s), 6.83 (1H, s), 7.60 (1H, s), 7.80 (1H, s).

The Present Compound 1-131

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.20 (3H, t, J=7.20 Hz), 1.67 (3H, d, J=6.90 Hz), 3.60 (3H, m), 4.18 (2H, q, J=7.09 Hz), 4.80 (1H, q, J=6.80 Hz), 6.40 (1H, s), 6.92 (1H, s), 8.02 (1H, s), 8.09 (1H, s).

The Present Compound 1-246

¹H-NMR (250 MHz, CDCl₃, TMS, δ (ppm)): 1.13 (3H, t, J=7.07 Hz), 1.55 (3H, d, J=7.25 Hz), 3.61-3.62 (3H, m), 3.96 (1H, q, J=7.14 Hz), 4.08-4.15 (2H, m), 6.42 (1H, s), 8.10 (1H, s), 8.28 (1H, s).

The Present Compound 1-285

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.61 (3H, m), 6.42 (1H, s), 7.72 (1H, s), 7.73 (1H, s), 7.98 (1H, s).

The Present Compound 1-289

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.61-3.62 (3H, m), 6.43 (1H, s), 7.81 (1H, d, J=1.26 Hz), 7.93 (1H, d, J=1.44 Hz), 8.02 (1H, s), 10.00 (1H, s).

The Present Compound 1-304

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.60 (3H, s), 3.94 (3H, s), 6.41 (1H, s), 7.97 (1H, s), 7.98 (1H, d, J=1.35 Hz), 8.09 (1H,d, J=1.35 Hz).

The Present Compound 1-305

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.59 (3H, m), 3.93 (3H, s), 6.40 (1H, s), 7.67 (1H, s), 7.87 (1H, s), 7.89 (1H, s).

The Present Compound 1-358

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 2.40 (3H, s), 3.59 (3H, m), 6.40 (1H, s), 7.01 (1H, s), 7.19 (1H, s), 7.85 (1H, s).

The Present Compound 1-361

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 2.67 (3H, s), 3.61 (3H, m), 6.42 (1H, s), 7.27 (1H, s), 8.03 (1H, s), 8.27 (1H, s).

The Present Compound 1-378

m.p.: 208.2° C.

The Present Compound 1-861

m.p.: 135.9° C.

The Present Compound 1-864

m.p.: 183.8° C.

The Present Compound 1-871

m.p.: 193.2° C.

The Present Compound 1-882

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.59-3.61 (3H, m), 6.42 (1H, s), 6.98 (1H, s), 7.85 (1H, s).

The Present Compound 1-887

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 3.61 (3H, s), 3.96 (1H, s), 6.44 (1H, s), 6.91 (1H, s), 7.94 (1H, s).

The Present Compound 1-892

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.41 (6H, d, J=6.3 Hz), 3.60 (3H, d, J=1.1 Hz), 4.56-4.68 (1H, m), 6.43 (1H, s), 6.91 (1H, s), 7.91 (1H, s).

The Present Compound 1-932

¹H-NMR (300 MHz, CDCl₃, TMS, δ (ppm)): 1.19 (3H, t, J=7.1 Hz), 1.73 (3H, d, J=7.0), 3.59-3.61 (3H, m), 4.14-4.23 (2H, m), 4.81 (1H, q, J=7.1 Hz), 6.42 (1H, s), 6.87 (1H, s), 7.96 (1H, s).

The following are Formulation Examples in which the present compounds are indicated by their compound numbers in Tables 1 to 54 and parts are by weight.

Formulation Example 1

Fifty parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2-2025, 3-1 to 3-50 and 3-2001 to 3-2025, 3 parts of calcium lignin sulfonate, 2 parts of sodium lauryl sulfate, and 45 parts of synthetic hydrated silicon oxide are well pulverized and mixed to give a wettable powder for each compound.

Formulation Example 2

Ten parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025, 3-1 to 3-50 and 3-2001 to 3-2025, 14 parts of polyoxyethylene styryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate, 35 parts of xylene, and 35 parts of cyclohexanone are well mixed to an emulsifiable concentrate for each compound.

Formulation Example 3

Two parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025, 3-1 to 3-50 and 3-2001 to 3-2025, 2 parts of synthetic hydrated silicon oxide, 2 parts of calcium lignin sulfonate, 30 parts of bentonite, and 64 parts of kaolin clay are well pulverized and mixed, and the mixture is well kneaded with water, followed by granulation and drying, to give a granule for each compound.

Formulation Example 4

Twenty-five parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2025, 3-1 to 3-50 and 3-2001 to 3-2025, 50 parts of 10% aqueous polyvinyl alcohol solution, and 25 parts of water are mixed and pulverized until the mean particle size reaches 5 μm or smaller to give a flowable for each compound.

Formulation Example 5

Five parts of each of the present compounds 1-1 to 1-992, 1-2001 to 1-2200, 2-1 to 2-50, 2-2001 to 2-2025, 3-1 to 3-50 and 3-2001 to 3-2025 is added to 40 parts of 10% aqueous polyvinyl alcohol solution, and the mixture is emulsified by dispersion with a homogenizer until the mean particle size reaches 10 μm or smaller, followed by addition of 55 parts of water, to give a concentrated emulsion for each compound

The following are Test Examples for demonstrating that the present compounds are useful as active ingredients of herbicides. In Test Examples, the present compounds are designated by their compound numbers in Tables 1 to 54.

Test Example 1

Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, seeded with velvetleaf (Abutilon theophrasti), and kept in a greenhouse for 14 days. After that, according to Formulation Example 2, compound 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-871, 1-877, 1-892, 1-2068, 2-4 or 2-2011 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water containing a spreading agent and then uniformly sprayed over the foliage of the plants with a sprayer at a ratio of 1000 liters per hectare. The pots were further kept in the greenhouse for 8 days and examined for herbicidal activity. As a result, it was found that compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-871, 1-877, 1-892, 1-2068, 2-4 and 2-2011 completely inhibited the growth of velvetleaf at a dosage of 2000 g/ha.

Test Example 2

Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil, seeded with velvetleaf (Abutilon theophrasti), and kept in a greenhouse for 14 days. After that, according to Formulation Example 2, compound 2-2001 or 3-2001 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water containing a spreading agent and then uniformly sprayed over the foliage of the plants with a sprayer at a ratio of 1000 liters per hectare. The pots were further kept in the greenhouse for 5 days and examined for herbicidal activity. As a result, it was found that compounds .2-2001 and 3-2001 completely killed velvetleaf at a dosage of 8000 g/ha.

Test Example 3

Cylindrical plastic pots of 10 cm in diameter and 10 cm in depth were filled with soil and seeded with velvetleaf (Abutilon theophrasti). According to Formulation Example 2, compound 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-877 or 1-892 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water and then uniformly sprayed over the surface of the soil in the pots with a sprayer at a ratio of 1000 liters per hectare. The pots were kept in a greenhouse for 9 days and examined for herbicidal activity. As a result, it was found that compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-24, 1-28, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-877 and 1-892 completely inhibited the germination of velvetleaf at a dosage of 2000 g/ha.

Test Example 4

Cylindrical plastic pots of 9 cm in diameter and 11 cm of depth were filled with soil, seeded with barnyardgrass (Echinochloa oryzicola), flooded into a paddy field, and kept in a greenhouse for 12 days. According to Formulation Example 2, compound 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-864, 1-877 or 1-892 was formulated into an emulsifiable concentrate, which was diluted in a prescribed amount with water and then applied on the water surface in the pots at a ratio of 50 liters per are. The pots were further kept in the greenhouse for 9 days and examined for herbicidal activity. As a result, it was found that compounds 1-1, 1-2, 1-3, 1-4, 1-5, 1-8, 1-9, 1-10, 1-11, 1-75, 1-82, 1-84, 1-86, 1-127, 1-129, 1-131, 1-201, 1-246, 1-282, 1-283, 1-289, 1-293, 1-303, 1-358, 1-361, 1-378, 1-407, 1-431, 1-861, 1-864, 1-877 and 1-892 completely inhibited the growth of barnyardgrass at a dosage of 1000 g/ha.

Industrial applicability

The condensed heterocyclic compounds of the present invention are useful as active ingredients of herbicides because of their excellent herbicidal activity. 

What is claimed is:
 1. A condensed heterocyclic compound of general formula I

wherein T is carbon and the bond between T and A is a double bond, the bond between A and Y is a single bond, and Y is oxygen; A is C—R¹⁴¹ wherein R¹⁴¹ is hydrogen; R¹ is hydrogen, halogen, C₁-C₃ alkyl, C₁-C₃ haloalkyl, hydroxymethyl, nitro, or cyano; R² is hydrogen, halogen, C₁-C₁₁, alkyl C₁-C₁₁ haloalkyl, hydroxymethyl, nitro, cyano, —N(R⁹)R¹⁹, —OR^(11, —SR) ¹², —SO₂R¹³, —COX, —COOR¹⁴, —CON(R¹⁵)R¹⁶, —COOR¹⁷, —C(R²⁶)═NOR¹⁹, —C(R²⁷)═C(R²¹)R²², or —OH(R²³)—CH(R²⁴)R²⁵; R³ is hydrogen, halogen, C₁-C₁₁ alkyl, C₁-C₁₁ haloalkyl, hydroxymethyl, nitro, cyano, —N(R⁵⁹)R⁶⁰, —OR⁶¹, —SR⁶², —SO₂R⁶³, —COX, —COOR⁶⁴, —CON(R⁶⁵)R⁶⁶, —COR⁶⁷, —C(R⁷⁶)═CR⁶⁹, —C(R⁷⁷)═C(R⁷¹)R⁷², or —CH(R⁷³)—CH(R⁷⁴)R⁷⁵; R⁴ is hydrogen, halogen, C₁-C₃, alkyl, C₁-C₃ haloalkyl, hydroxymethyl, nitro, or cyano;  wherein X is chlorine or bromine; R⁹ and R⁵⁹ are independently hydrogen, C₁-C₅ alkyl, (C₁-C₅ alkyl)carbonyl, or (C₁-C₅ alkoxy) carbonyl; R¹⁰, R¹¹, and R¹² are independently hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, cyano C₁-C₆ alkyl, (C₁-C₅ alkyl)carbonyl, (C₁-C₅ haloalkyl)carbonyl, (C₃-C₁₀ cycloalkyl)carbonyl, (C₁-C₅ alkyl)carbonyl C₁-C₅ alkyl, (C₁-C₅ haloalkyl)carbonyl C₁-C₅ alkyl, hydroxy C₁-C₅ alkyl, C₁-C₅ alkoxy C₁-C₅ alkyl, C₁-C₅ alkylthio C₁-C₅ alkyl, (C₁-C₅ alkoxy)carbonyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, —C(R⁴³) (R⁴⁴)—C(═O)ON(R⁴⁵)R⁴⁶, —C(R⁴⁷) (R⁴⁸)—CON(R⁴⁹)R⁵⁰, —CH₂—C(R⁵⁶)═N—OR⁵⁵, —CHMe—C(R⁵⁸)═NOR⁵⁷, (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkenoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, carboxy(C₁-C₅ alkyl)carbonyl, (C₁-C₁₀ alkoxy)carbonyl(C₁-C₅ alkyl)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl (C₁-C₅ alkyl)carbonyl, C₁-C₅ alkylsulfonyl, C₁-C₅ haloalkylsulfonyl, —SO₂N(R⁵¹)R⁵², —CON(R⁵³)R⁵⁴, optionally substituted benzyl, or optionally substituted phenyl; R⁶⁰, R⁶¹, and R⁶² are independently hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, cyano C₁-C₆ alkyl, (C₁-C₅ alkyl)carbonyl, (C₁-C₅ haloalkyl)carbonyl, (C₃-C₁₀ cycloalkyl)carbonyl, (C₁-C₅ alkyl)carbonyl C₁-C₅ alkyl, (C₁-C₅ haloalkyl)carbonyl C₁-C₅ alkyl, hydroxy C₁-C₅ alkyl, C₁-C₅ alkoxy C₁-C₅ alkyl, C₁-C₅ alkylthio C₁-C₅ alkyl, C₁-C₆ alkoxy)carbonyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, —C(R¹⁶³)(R¹⁶⁴)—C(═O)ON(R¹⁶⁵)R¹⁶⁶, —C(R¹⁶⁷)(R¹⁶⁸)—CON(R¹⁶⁹)R¹⁷⁰, —CH₂—C(═NOR¹⁷⁵)R¹⁷⁶, —CHMe—C(═NOR¹⁷⁷)R¹⁷⁸, (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl, phenoxycarbonyl, benzyloxycarbonyl, carboxy(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkenoxy)carbonyl(C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl (C₁-C₅ alkoxy)carbonyl C₁-C₅ alkyl, carboxy(C₁-C₅ alkyl)carbonyl, (C₁-C₁₀ alkoxy)carbonyl(C₁-C₅ alkyl)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl(C₁-C₅ alkyl)carbonyl, C₁-C₅ alkylsulfonyl, C₁-C₅ haloalkylsulfonyl, —SO₂N(R¹⁷¹)R¹⁷², —CON(R¹⁷³)R¹⁷⁴, optionally substituted benzyl, or optionally substituted phenyl;  wherein R⁴³, R⁴⁴, R¹⁶³, and R¹⁶⁴ are independently hydrogen, halogen, C₁-C₅ alkyl, or C₁-C₅ haloalkyl; R⁴⁵, R⁴⁶, R¹⁶⁵, and R¹⁶⁶ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁴⁵ and R⁴⁶ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated rind, or R¹⁶⁵ and R¹⁶⁶ may be combined at their ends to form together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; R⁴⁷, R⁴⁸, R¹⁶⁷, and R¹⁶⁸ are independently hydrogen, halogen, C₁-C₅ alkyl, or C₁-C₅ haloalkyl; R⁴⁹, R⁵⁰, R¹⁶⁹, and R¹⁷⁰ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁴⁹ and R⁵⁰ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R¹⁶⁹ and R¹⁷⁰ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; P⁵¹, R⁵², R¹⁷¹ and R¹⁷² are independently hydrogen, C₁-C₅ alkyl C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl; or C₃-C₆ alkynyl; or R⁵¹ and R⁵² may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R¹⁷¹ and ¹⁷² may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R⁵³, R⁵⁴, R¹⁷³, and R¹⁷⁴ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkynyl, or C₃-C₆ alkynyl; or R⁵³ and R⁵⁴ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring, or R¹⁷³ and R¹⁷⁴ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R⁵⁵, R⁵⁷, R¹⁷⁵, and R¹⁷⁷ are independently hydrogen or C₁-C₃ alkyl; R⁵⁶, R⁵⁸, R¹⁷⁶, and R¹⁷⁸ are independently hydrogen, C₁-C₅ alkyl, (C₁-C₅ alkoxy)carbonyl, (C₁-C₅ haloalkoxy)carbonyl, (C₃-C₅ cycloalkoxy)carbonyl, (C₃-C₅ alkenoxy)carbonyl, or (C₃-C₅ alkynoxy)carbonyl; R¹³ is hydroxy, chlorine, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl, C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, —N(R⁷⁹)R⁸⁰, or —OR⁸¹; R⁶³ hydroxy, chlorine, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl, C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, —N(R¹⁷⁹)R¹⁸⁰, or —OR¹⁸¹;  wherein R⁷⁹ and R¹⁷⁹ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl, C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R⁸⁰ and R¹⁸⁰ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁷⁹ and R⁸⁰ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R¹⁷⁹ and R¹⁸⁰ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- or 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; and R⁸¹ and R¹⁸¹ are independently C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R¹⁴ is hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkenoxy) carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl, —N(R⁸²)R⁸³, optionally substituted benzyl, or optionally substituted phenyl; R⁶⁴ is hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkenoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ alkynoxy)carbonyl C₁-C₅ alkyl, —N(R¹⁸²)R¹⁸³, optionally substituted benzyl, or optionally substituted phenyl; wherein R⁸² and R¹⁸² are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R⁸³ sand R¹⁸³ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁸² and R⁸³ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R¹⁸² and R¹⁸³ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R¹⁵ and R⁶⁵ are independently hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ alkynyl, cyano C₁-C₆ alkyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, optionally substituted benzyl, or optionally substituted phenyl; R¹⁶ and R⁵⁶ are independently hydrogen, C₁-C₁₀ alkyl, or C₁-C₁₀ haloalkyl; or R¹⁵ and R¹⁶ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R⁶⁵ and R⁶⁶ may be, combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R¹⁷, R²⁶, R²⁷, R⁶⁷, R⁷⁶, and R⁷⁷ are independently hydrogen, cyano, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, (C₁-C₆ alkoxy)carbonyl, or (C₁-C₆ alkoxy)carbonylmethyl; R¹⁹ and R⁶⁹ are independently hydrogen, C₁-C₁₀ alkyl, C₁-C₁₀ haloalkyl, C₃-C₁₀ cycloalkyl, C₃-C₁₀ halocycloalkyl, C₃-C₁₀ cycloalkyl C₁-C₃ alkyl, C₃-C₁₀ alkenyl, C₃-C₁₀ haloalkenyl, C₃-C₁₀ alkynyl, C₃-C₁₀ haloalkynyl, cyano C₁-C₆ alkyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R²¹ and R⁷¹ are independently hydrogen, halogen, C₁-C₃ alkyl, or C₁-C₃ haloalkyl; R²² and R²⁵ are independently carboxy, (C₁-C₁₀ alkoxy)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl, (C₃-C₁₀ cyrloalkoxy)carbonyl (C₃-C₁₀ halocycloalkoxy)carbonyl, carboxy(C₁-C₅ alkoxy)carbonyl, (C₁-C₁₀ alkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ cycloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ alkenoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ alkynoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, —CON(R⁸⁴)R⁸⁵, or —C(═O)ON(R⁸⁶)R⁸⁷; R⁷² and R⁷⁵ are independently carboxy, (C₁-C₁₀ alkoxy)carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl, (C₃-C₁₀ cycloalkoxy)carbonyl, (C₃-C₁₀ halocycloalkoxy)carbonyl, carboxy(C₁-C₅ alkoxy)carbonyl, (C₁-C₁₀ alkoxy)carbonyl (C₁-C₅ alkoxy) carbonyl, (C₁-C₁₀ haloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ cycloalkoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ alkenoxy)carbonyl (C₁-C₅ alkoxy)carbonyl, (C₃-C₁₀ alkynoxy)carbonyl (C₁-C₅ alkoxy carbonyl, —CON(R¹⁸⁴)R¹⁸⁵, or —C(═O)ON(R¹⁸⁶)R¹⁸⁷;  wherein R⁸⁴ and R¹⁸⁴ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, (C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R⁸⁵ and R¹⁸⁵ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁸⁴ and R⁸⁵ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; or R¹⁸⁴ and R¹⁸⁵ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring containing zero to one oxygen atom or NH group in the ring; R⁸⁶ and R¹⁸⁶ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, carboxy C₁-C₅ alkyl, (C₁-C₁₀ alkoxy)carbonyl C₁-C₅ alkyl, (C₁-C₁₀ haloalkoxy)carbonyl C₁-C₅ alkyl, (C₃-C₁₀ cycloalkoxy)carbonyl C₁-C₅ alkyl, or (C₃-C₁₀ halocycloalkoxy)carbonyl C₁-C₅ alkyl; R⁸⁷ and R¹⁸⁷ are independently hydrogen, C₁-C₅ alkyl, C₁-C₅ haloalkyl, C₃-C₈ cycloalkyl, C₃-C₆ alkenyl, or C₃-C₆ alkynyl; or R⁸⁶ and R⁸⁷ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; or R¹⁸⁶ and R¹⁸⁷ may be combined at their ends to form, together with the adjacent nitrogen atom, a 3- to 7-membered saturated ring; R²³, R²⁴, R⁷³, and R⁷⁴ are independently hydrogen, halogen, C₁-C₃ alkyl, or C₁-C₃ haloalkyl; and Q is any one group of Q14, Q15, or Q17 of the general formula:

 wherein: in Q14, E²⁵ is hydrogen, C₁-C₃ alkyl, or halogen; E²⁶ is C₁-C₃ alkyl optionally substituted with halogen; E²⁷ is hydrogen, amino, C₁-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, or optionally substituted benzyl; and D⁷ is oxygen or sulfur; in Q15, E²⁸ is C₁-C₃ alkyl optionally substituted with halogen; E²⁹ is hydrogen, amino, C₁-C₆ alkyl, C₃-C₆ alkenyl, C₃-C₆ alkynyl, or optionally substituted benzyl; and Do is oxygen or sulfur; and in Q17, E³² is C₁-C₃ alkyl optionally substituted with halogen; E³³ is hydrogen, halogen, amino, C₁-C₃ alkyl optionally substituted with halogen, C₁-C₃ alkoxy optionally substituted with halogen, or C₁-C₃ alkylthio optionally substituted with halogen; and E⁴³ is hydrogen or C₁-C₃ alkyl optionally substituted with halogen.
 2. The condensed heterocyclic compound according to claim 1, wherein Q is Q14.
 3. The condensed heterocyclic compound according to claim 1, wherein Q is Q15.
 4. The condensed heterocyclic compound according to claim 1, wherein Q is Q1, of which E¹ and E² are combined at their ends to form C₂-C₆ alkylene (which alkylene may optionally be substituted with methyl or halogen) or C₂-C₅ alkenylene (which alkenylene may optionally be substituted with methyl or halogen); or Q is Q2, of which E³ and E⁴ are combined at their ends to form C₂-C₅ alkylene (which alkylene may optionally be substituted with methyl or halogen) or C₂-C₅ alkenylene (which alkenylene may optionally be substituted with methyl or halogen), and D¹ and Z¹ are as defined above; or Q is Q4, of which E⁶ is C₁-C₆ alkyl optionally substituted with halogen and E⁷ is C₁-C₆ alkyl optionally substituted with halogen; or Q is Q4, of which E⁶ and E⁷ are combined at their ends to form C₂-C₅ alkylene (which alkylene may optionally be substituted with methyl or halogen) or C₂-C₅ alkenylene (which alkenylene may optionally be substituted with methyl or halogen); or Q is Q6, of which E⁴⁴ is chlorine or bromine, E¹⁰ is C₁-C₆ alkyl optionally substituted with halogen, and E¹¹ is C₁-C₆ alkyl optionally substituted with halogen; or Q is Q6, of which E⁴⁴ is chlorine or bromine, and E¹⁰ and E¹¹ are combined at their ends to form C₂-C₅ alkylene (which alkylene may optionally be substituted with methyl or halogen) or C₂-C₅ alkenylene (which alkylene may optionally be substituted with methyl or halogen).
 5. The condensed heterocyclic compound according to claim 1, wherein Q is Q1, of which E¹ and E² are combined at their ends to form tetramethylene (which tetramethylene may optionally be substituted with methyl or halogen); or Q is Q2, of which E³ and E⁴ are combined at their ends to form tetramethylene (which tetramethylene may optionally be substituted with methyl or halogen), D¹ is oxygen, and Z¹ is nitrogen; or Q is Q4, of which E⁶ is methyl substituted with fluorine, or ethyl substituted with fluorine, and E⁷ is methyl or ethyl; or Q is Q4, of which E⁶ and E⁷ are combined at their ends to form tetramethylene (which tetramethylene may optionally be substituted with methyl or halogen); or Q is Q6, of which E⁴⁴ is chlorine or bromine, E¹⁰ is methyl substituted with fluorine, or ethyl substituted with fluorine, and E¹¹ is methyl or ethyl; or Q is Q6, of which E¹⁰ and E¹¹ are combined at their ends to form tetramethylene (which tetramethylene may optionally be substituted with methyl or halogen).
 6. The condensed heterocyclic compound according to claim 1, wherein Q is Q17.
 7. The condensed heterocyclic compound according to claim 1, wherein Q is Q14, of which E²⁵ is hydrogen, E²⁶ is C₁-C₃ alkyl optionally substituted with halogen, E²⁷ is C₁-C₃ alkyl, and D⁷ is oxygen.
 8. The condensed heterocyclic compound according to claim 1, wherein Q is Q14, of which E²⁵ is hydrogen, E²⁶ is methyl substituted with fluorine, or ethyl substituted with fluorine, E²⁷ is methyl or ethyl, and D⁷ is oxygen.
 9. The condensed heterocyclic compound according to any one of claims 1, 2, 3, 4, 5, 6, 7, or 8 wherein A s nitrogen, CH, CCH₃, CCl, or CBr.
 10. The condensed heterocyclic compound according to claim 1, wherein R¹ is hydrogen or halogen.
 11. The condensed heterocyclic compound according to claim 1, wherein T is nitrogen.
 12. The condensed heterocyclic compound according to claim 1, wherein R² is hydrogen, halogen, C₁-C₁₁ alkyl, nitro, cyano, —N(R⁹)R¹⁰, —OR¹¹, —SR¹², COOR¹⁴, —CON(R¹⁵)R¹⁶, —COR¹⁷, —C(R²⁶)═NOR¹⁹, —C(R²⁷)═C(R²¹)R²², or —CH(R²³)—CH(R²⁴)R²⁵.
 13. The condensed heterocyclic compound according to claim 1, wherein R³ is hydrogen, halogen, or nitro.
 14. The condensed heterocyclic compound according to claim 1, wherein R⁴ is hydrogen or halogen.
 15. The condensed heterocyclic compound according to claim 1, wherein T is carbon, A is CH, Y is oxygen, R¹ is hydrogen, Q is Q14, E²⁵ is hydrogen, E²⁶ is trifluoromethyl, and E²⁷ is methyl.
 16. A herbicidal composition comprising a condensed heterocyclic compound according to claim 1, and an inert carrier or diluent.
 17. A method for controlling weeds, which comprises applying an effective amount of a condensed heterocyclic compound according to claim 1, to weeds or to a place where weeds are growing or will grow. 